Feature

When prescribing glucagon-like peptide 1 (GLP-1) medications, many physicians prefer tirzepatide over the more well-known semaglutide due to its superior efficacy in weight loss and A1c reduction. Studies indicated that tirzepatide can lead to greater weight loss than semaglutide.

Factors like insurance coverage, drug availability, and side effects also influence physicians’ choices, with some patients benefiting from the broader dosing options that tirzepatide offers.

In this Q&A, Medscape Medical News explored how physicians can make the best decisions with their patients when choosing between GLP-1 medications tirzepatide and semaglutide for the treatment for type 2 diabetes and obesity.

We spoke to physicians who specialize in medical weight loss on things to consider when choosing between these two medications, such as patient profiles, drug access and availability, and financial considerations. We also discussed the side effect profiles of the medications based on current data in the literature.
 

Medscape Medical News: How are you deciding which of the two drugs to prescribe?

Caroline Messer, MD, endocrinologist at Lenox Hill Hospital, Northwell, New York City: To some degree, it’s based on insurance. But in general, I’m pushing most patients toward tirzepatide just because the data show that there’s more weight loss and more A1c reduction on tirzepatide. But the research shows that there are more side effects. But I think every practicing clinician who uses these medications knows that there are actually fewer side effects despite what the trial showed.

Sue Decotiis, MD, weight loss doctor, New York City: I think that many doctors that are prescribing these drugs are not really weight loss specialists. It’s just like one of many drugs that they prescribe. And semaglutide (Ozempic) is more well known. I think it’s because they don’t really know that it’s not as good as the other drugs. There are still massive shortages of these drugs. So that’s another reason why a doctor may choose one drug over another. Also, if a patient’s reliant on insurance to cover it, they may go with whatever the insurance company is willing to cover.

Kathleen Dungan, MD, professor of internal medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University Wexner Medical Center and College of Medicine: Some patients may have preferences with the delivery device. In the past year, in particular, availability of these drugs was limited and varied from time to time and geographically, and therefore, patients needed to substitute one drug for another in order to maintain treatment.

Maria Teresa Anton, MD, endocrinologist and educator, Pritikin Longevity Center, Miami: While I do not prescribe these medications, I do focus on integrating them into a comprehensive lifestyle program that empowers patients to make sustainable changes. By fostering an environment of education and support, we enhance their well-being and promote long-term health outcomes. In my practice, I’ve found that the most successful outcomes occur when these medications are combined with a comprehensive approach, including dietary changes, physical activity, and behavioral support.
 

Medscape Medical News: How do you make the decision of tirzepatide vs semaglutide?

Messer: There’s no guideline per se. Sometimes when I don’t want a patient to lose too much weight, I might consider Ozempic or Wegovy if you know they only have 5 lb to lose. If diabetes, then I might go for the Ozempic instead, just because the weight loss is so drastic with tirzepatide with any kind of appetite.

Decotiis: If somebody has a lot of weight to lose and they’re highly insulin resistant, as most people are when they start these drugs, I really prefer tirzepatide ... because I think patients are going to lose more weight, they’re going to lose more fat. I also see that patients have less side effects because before tirzepatide came out, I was prescribing mostly semaglutide, and there were a lot of side effects. But semaglutide is fine. I mean, it’s a good drug. Maybe it’s better for people that don’t have as much weight to lose. So I don’t have to worry about them hitting that wall after a certain period of time. But it’s a good drug. I mean, I certainly still use it.
 

Medscape Medical News: What of the data and the literature on the differences in the outcomes and the side effect profile?

Messer: In terms of outcomes, the weight loss is almost double [with tirzepatide]. It depends what trial you’re looking at, but we tend to see like about 15% of your body weight you lose with the semaglutide and 25%-30% with the tirzepatide. The big difference, I suppose…is semaglutide now has a cardiovascular indication and the tirzepatide doesn’t, but I’m very confident that tirzepatide is going to get the same indication.

Decotiis: When that first Lilly study came out in June of 2022, it really blew everybody away. I mean, some patients lost up to 25% of their weight on tirzepatide, whereas on Ozempic, it was really like 15%. Now, in my practice, I really monitor everyone with a body composition scale. I’m not just looking at somebody’s weight or body mass index, I am looking at how much body fat they have, how much muscle mass they have, how much water they have, and how much bone they have.

The golden rule here is make sure the patient loses fat, and you want to make sure they’re not losing muscle or too much water. The patient really needs to be adequately hydrated. So what I’m saying is a lot of people who have lost weight have not reached the promised land because they haven’t lost enough body fat to get them into that healthy zone. But once they reduce the body fat to a certain percentage, let’s say for a woman about 20%, or a man in the low teens, they’re less likely to regain that weight because they haven’t really lost fat. And that’s how we gain health.
 

A version of this article first appeared on Medscape.com.

When prescribing glucagon-like peptide 1 (GLP-1) medications, many physicians prefer tirzepatide over the more well-known semaglutide due to its superior efficacy in weight loss and A1c reduction. Studies indicated that tirzepatide can lead to greater weight loss than semaglutide.

Factors like insurance coverage, drug availability, and side effects also influence physicians’ choices, with some patients benefiting from the broader dosing options that tirzepatide offers.

In this Q&A, Medscape Medical News explored how physicians can make the best decisions with their patients when choosing between GLP-1 medications tirzepatide and semaglutide for the treatment for type 2 diabetes and obesity.

We spoke to physicians who specialize in medical weight loss on things to consider when choosing between these two medications, such as patient profiles, drug access and availability, and financial considerations. We also discussed the side effect profiles of the medications based on current data in the literature.
 

Medscape Medical News: How are you deciding which of the two drugs to prescribe?

Caroline Messer, MD, endocrinologist at Lenox Hill Hospital, Northwell, New York City: To some degree, it’s based on insurance. But in general, I’m pushing most patients toward tirzepatide just because the data show that there’s more weight loss and more A1c reduction on tirzepatide. But the research shows that there are more side effects. But I think every practicing clinician who uses these medications knows that there are actually fewer side effects despite what the trial showed.

Sue Decotiis, MD, weight loss doctor, New York City: I think that many doctors that are prescribing these drugs are not really weight loss specialists. It’s just like one of many drugs that they prescribe. And semaglutide (Ozempic) is more well known. I think it’s because they don’t really know that it’s not as good as the other drugs. There are still massive shortages of these drugs. So that’s another reason why a doctor may choose one drug over another. Also, if a patient’s reliant on insurance to cover it, they may go with whatever the insurance company is willing to cover.

Kathleen Dungan, MD, professor of internal medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University Wexner Medical Center and College of Medicine: Some patients may have preferences with the delivery device. In the past year, in particular, availability of these drugs was limited and varied from time to time and geographically, and therefore, patients needed to substitute one drug for another in order to maintain treatment.

Maria Teresa Anton, MD, endocrinologist and educator, Pritikin Longevity Center, Miami: While I do not prescribe these medications, I do focus on integrating them into a comprehensive lifestyle program that empowers patients to make sustainable changes. By fostering an environment of education and support, we enhance their well-being and promote long-term health outcomes. In my practice, I’ve found that the most successful outcomes occur when these medications are combined with a comprehensive approach, including dietary changes, physical activity, and behavioral support.
 

Medscape Medical News: How do you make the decision of tirzepatide vs semaglutide?

Messer: There’s no guideline per se. Sometimes when I don’t want a patient to lose too much weight, I might consider Ozempic or Wegovy if you know they only have 5 lb to lose. If diabetes, then I might go for the Ozempic instead, just because the weight loss is so drastic with tirzepatide with any kind of appetite.

Decotiis: If somebody has a lot of weight to lose and they’re highly insulin resistant, as most people are when they start these drugs, I really prefer tirzepatide ... because I think patients are going to lose more weight, they’re going to lose more fat. I also see that patients have less side effects because before tirzepatide came out, I was prescribing mostly semaglutide, and there were a lot of side effects. But semaglutide is fine. I mean, it’s a good drug. Maybe it’s better for people that don’t have as much weight to lose. So I don’t have to worry about them hitting that wall after a certain period of time. But it’s a good drug. I mean, I certainly still use it.
 

Medscape Medical News: What of the data and the literature on the differences in the outcomes and the side effect profile?

Messer: In terms of outcomes, the weight loss is almost double [with tirzepatide]. It depends what trial you’re looking at, but we tend to see like about 15% of your body weight you lose with the semaglutide and 25%-30% with the tirzepatide. The big difference, I suppose…is semaglutide now has a cardiovascular indication and the tirzepatide doesn’t, but I’m very confident that tirzepatide is going to get the same indication.

Decotiis: When that first Lilly study came out in June of 2022, it really blew everybody away. I mean, some patients lost up to 25% of their weight on tirzepatide, whereas on Ozempic, it was really like 15%. Now, in my practice, I really monitor everyone with a body composition scale. I’m not just looking at somebody’s weight or body mass index, I am looking at how much body fat they have, how much muscle mass they have, how much water they have, and how much bone they have.

The golden rule here is make sure the patient loses fat, and you want to make sure they’re not losing muscle or too much water. The patient really needs to be adequately hydrated. So what I’m saying is a lot of people who have lost weight have not reached the promised land because they haven’t lost enough body fat to get them into that healthy zone. But once they reduce the body fat to a certain percentage, let’s say for a woman about 20%, or a man in the low teens, they’re less likely to regain that weight because they haven’t really lost fat. And that’s how we gain health.
 

A version of this article first appeared on Medscape.com.

When prescribing glucagon-like peptide 1 (GLP-1) medications, many physicians prefer tirzepatide over the more well-known semaglutide due to its superior efficacy in weight loss and A1c reduction. Studies indicated that tirzepatide can lead to greater weight loss than semaglutide.

Factors like insurance coverage, drug availability, and side effects also influence physicians’ choices, with some patients benefiting from the broader dosing options that tirzepatide offers.

In this Q&A, Medscape Medical News explored how physicians can make the best decisions with their patients when choosing between GLP-1 medications tirzepatide and semaglutide for the treatment for type 2 diabetes and obesity.

We spoke to physicians who specialize in medical weight loss on things to consider when choosing between these two medications, such as patient profiles, drug access and availability, and financial considerations. We also discussed the side effect profiles of the medications based on current data in the literature.
 

Medscape Medical News: How are you deciding which of the two drugs to prescribe?

Caroline Messer, MD, endocrinologist at Lenox Hill Hospital, Northwell, New York City: To some degree, it’s based on insurance. But in general, I’m pushing most patients toward tirzepatide just because the data show that there’s more weight loss and more A1c reduction on tirzepatide. But the research shows that there are more side effects. But I think every practicing clinician who uses these medications knows that there are actually fewer side effects despite what the trial showed.

Sue Decotiis, MD, weight loss doctor, New York City: I think that many doctors that are prescribing these drugs are not really weight loss specialists. It’s just like one of many drugs that they prescribe. And semaglutide (Ozempic) is more well known. I think it’s because they don’t really know that it’s not as good as the other drugs. There are still massive shortages of these drugs. So that’s another reason why a doctor may choose one drug over another. Also, if a patient’s reliant on insurance to cover it, they may go with whatever the insurance company is willing to cover.

Kathleen Dungan, MD, professor of internal medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University Wexner Medical Center and College of Medicine: Some patients may have preferences with the delivery device. In the past year, in particular, availability of these drugs was limited and varied from time to time and geographically, and therefore, patients needed to substitute one drug for another in order to maintain treatment.

Maria Teresa Anton, MD, endocrinologist and educator, Pritikin Longevity Center, Miami: While I do not prescribe these medications, I do focus on integrating them into a comprehensive lifestyle program that empowers patients to make sustainable changes. By fostering an environment of education and support, we enhance their well-being and promote long-term health outcomes. In my practice, I’ve found that the most successful outcomes occur when these medications are combined with a comprehensive approach, including dietary changes, physical activity, and behavioral support.
 

Medscape Medical News: How do you make the decision of tirzepatide vs semaglutide?

Messer: There’s no guideline per se. Sometimes when I don’t want a patient to lose too much weight, I might consider Ozempic or Wegovy if you know they only have 5 lb to lose. If diabetes, then I might go for the Ozempic instead, just because the weight loss is so drastic with tirzepatide with any kind of appetite.

Decotiis: If somebody has a lot of weight to lose and they’re highly insulin resistant, as most people are when they start these drugs, I really prefer tirzepatide ... because I think patients are going to lose more weight, they’re going to lose more fat. I also see that patients have less side effects because before tirzepatide came out, I was prescribing mostly semaglutide, and there were a lot of side effects. But semaglutide is fine. I mean, it’s a good drug. Maybe it’s better for people that don’t have as much weight to lose. So I don’t have to worry about them hitting that wall after a certain period of time. But it’s a good drug. I mean, I certainly still use it.
 

Medscape Medical News: What of the data and the literature on the differences in the outcomes and the side effect profile?

Messer: In terms of outcomes, the weight loss is almost double [with tirzepatide]. It depends what trial you’re looking at, but we tend to see like about 15% of your body weight you lose with the semaglutide and 25%-30% with the tirzepatide. The big difference, I suppose…is semaglutide now has a cardiovascular indication and the tirzepatide doesn’t, but I’m very confident that tirzepatide is going to get the same indication.

Decotiis: When that first Lilly study came out in June of 2022, it really blew everybody away. I mean, some patients lost up to 25% of their weight on tirzepatide, whereas on Ozempic, it was really like 15%. Now, in my practice, I really monitor everyone with a body composition scale. I’m not just looking at somebody’s weight or body mass index, I am looking at how much body fat they have, how much muscle mass they have, how much water they have, and how much bone they have.

The golden rule here is make sure the patient loses fat, and you want to make sure they’re not losing muscle or too much water. The patient really needs to be adequately hydrated. So what I’m saying is a lot of people who have lost weight have not reached the promised land because they haven’t lost enough body fat to get them into that healthy zone. But once they reduce the body fat to a certain percentage, let’s say for a woman about 20%, or a man in the low teens, they’re less likely to regain that weight because they haven’t really lost fat. And that’s how we gain health.
 

A version of this article first appeared on Medscape.com.

Twice a month, a 40-foot-long truck transformed into a mobile clinic travels the Rio Grande Valley to provide rural Texans with women’s health care, including birth control.

The clinic, called the UniMóvil, is part of the Healthy Mujeres program at the University of Texas Rio Grande Valley School of Medicine in Edinburg.

The United States has about 3000 mobile health programs. But Saul Rivas, an ob.gyn., said he wasn’t aware of any that shared the specific mission of Healthy Mujeres when he helped launch the initiative in 2017. “Mujeres” means “women” in Spanish.

It’s now part of a small but growing number of mobile programs aimed at increasing rural access to women’s health services, including long-acting reversible contraception.

There are two kinds of these highly effective methods: intrauterine devices, known as IUDs, and hormonal implants inserted into the upper arm. These birth control options can be especially difficult to obtain — or have removed — in rural areas.

“Women who want to prevent an unintended pregnancy should have whatever works best for them,” said Kelly Conroy, senior director of mobile and maternal health programs at the University of Arkansas for Medical Sciences, Little Rock.

The school is launching a mobile women’s health and contraception program in rural parts of the state in October.

Rural areas have disproportionately fewer doctors, including ob.gyns., than urban areas. And rural providers may not be able to afford to stock long-acting birth control devices or may not be trained in administering them, program leaders say.

Mobile clinics help shrink that gap in rural care, but they can be challenging to operate, said Elizabeth Jones, a senior director at the National Family Planning & Reproductive Health Association.

Money is the greatest obstacle, Jones said. The Texas program costs up to $400,000 a year. A 2020 study of 173 mobile clinics found they cost an average of more than $630,000 a year. Mobile dental programs were the most expensive, averaging more than $1 million.

While many programs launch with the help of grants, they can be difficult to sustain, especially with over a decade of decreased or stagnant funding to Title X, a federal money stream that helps low-income people receive family planning services.

For example, a mobile contraception program serving rural Pennsylvania lasted less than 3 years before closing in 2023. It shut down after losing federal funding, said a spokesperson for the clinic that ran it.

Rural mobile programs aren’t as efficient or profitable as brick-and-mortar clinics. That’s because staff members may have to make hours-long trips to reach towns where they’ll probably see fewer patients than they would at a traditional site, Jones said.

She said organizations that can’t afford mobile programs can consider setting up “pop-up clinics” at existing health and community sites in rural areas.

Maria Briones is a patient who has benefited from the Healthy Mujeres program in southern Texas. The 41-year-old day care worker was concerned because she wasn’t getting her menstrual period with her IUD.

She considered going to Mexico to have the device removed because few doctors take her insurance on the US side of the Rio Grande Valley.

But Briones learned that the UniMóvil was visiting a small Texas city about 20 minutes from her home. She told the staff there that she doesn’t want more kids but was worried about the IUD.

Briones decided to keep the device after learning it’s safe and normal not to have periods while using an IUD. She won’t get billed for her appointment with the mobile clinic, even though the university health system doesn’t take her insurance.

“They have a lot of patience, and they answered all the questions that I had,” Briones said.

IUDs and hormonal implants are highly effective and can last up to 10 years. But they’re also expensive — devices can cost more than $1,000 without insurance — and inserting an IUD can be painful.

Patient-rights advocates are also concerned that some providers pressure people to use these devices.

They say ethical birth control programs aim to empower patients to choose the contraceptive method — if any — that is best for them, instead of promoting long-acting methods in an attempt to lower birth and poverty rates. They point to the history of eugenics-inspired sterilization and even more recent incidents.

For example, an investigation by Time magazine found doctors are more likely to push Black, Latina, young, and low-income women than other patients to use long-acting birth control — and to refuse to remove the devices.

Rivas said Healthy Mujeres staffers are trained on this issue.

“Our goal isn’t necessarily to place IUDs and implants,” he said. It’s to “provide education and help patients make the best decisions for themselves.”

David Wise, a spokesperson for the University of Arkansas for Medical Sciences, said staff members with the university’s mobile program will ask patients if they want to get pregnant in the next year, and will support their choice. The Arkansas and Texas programs also remove IUDs and hormonal arm implants if patients aren’t happy with them.

The Arkansas initiative will visit 14 rural counties with four vehicles the size of food trucks that were used in previous mobile health efforts. Staffing and equipment will be covered by a 2-year, $431,000 grant from an anonymous donor, Wise said.

In addition to contraception, faculty and medical residents staffing the vehicles will offer women’s health screenings, vaccinations, prenatal care, and testing and treatment for sexually transmitted infections.

Rivas said the Texas program was inspired by a study that found that, 6 months after giving birth, 34% of surveyed Texas mothers said long-acting contraception is their preferred birth control option — but only 13% were using that method.

“We started thinking about ways to address that gap,” Rivas said.

Healthy Mujeres, which is funded through multiple grants, started with a focus on contraception. It later expanded to services such as pregnancy ultrasounds, cervical cancer screenings, and testing for sexually transmitted infections.

While the Texas and Arkansas programs can bill insurance, they also have funding to help uninsured and underinsured patients afford their services. Both use community health workers — called promotoras in largely Spanish-speaking communities like the Rio Grande Valley — to connect patients with food, transportation, additional medical services, and other needs.

They partner with organizations that locals trust, such as food pantries and community colleges, which let the mobile units set up in their parking lots. And to further increase the availability of long-acting contraception in rural areas, the universities are training their students and local providers on how to insert, remove, and get reimbursed for the devices.

One difference between the programs is dictated by state laws. The Arkansas program can provide birth control to minors without a parent or guardian’s consent. But in Texas, most minors need consent before receiving health care, including contraception.

Advocates say these initiatives might help lower the rates of unintended and teen pregnancies in both states, which are higher than the national average.

Rivas and Conroy said their programs haven’t received much pushback. But Rivas said some churches that had asked the UniMóvil to visit their congregations changed their minds after learning the services included birth control.

Catherine Phillips, director of the Respect Life Office at Arkansas’ Catholic diocese, said the diocese supports efforts to achieve health care equity and she’s personally interested in mobile programs that visit rural areas such as where she lives.

But Phillips said the Arkansas program’s focus on birth control, especially long-acting methods, violates the teachings of the Catholic Church. Offering these services to minors without parental consent “makes it more egregious,” she said.

Jones said that, while these programs have hefty costs and other challenges, they also have benefits that can’t be measured in numbers.

“Building community trust and making an impact in the communities most impacted by health inequities — that’s invaluable,” she said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Twice a month, a 40-foot-long truck transformed into a mobile clinic travels the Rio Grande Valley to provide rural Texans with women’s health care, including birth control.

The clinic, called the UniMóvil, is part of the Healthy Mujeres program at the University of Texas Rio Grande Valley School of Medicine in Edinburg.

The United States has about 3000 mobile health programs. But Saul Rivas, an ob.gyn., said he wasn’t aware of any that shared the specific mission of Healthy Mujeres when he helped launch the initiative in 2017. “Mujeres” means “women” in Spanish.

It’s now part of a small but growing number of mobile programs aimed at increasing rural access to women’s health services, including long-acting reversible contraception.

There are two kinds of these highly effective methods: intrauterine devices, known as IUDs, and hormonal implants inserted into the upper arm. These birth control options can be especially difficult to obtain — or have removed — in rural areas.

“Women who want to prevent an unintended pregnancy should have whatever works best for them,” said Kelly Conroy, senior director of mobile and maternal health programs at the University of Arkansas for Medical Sciences, Little Rock.

The school is launching a mobile women’s health and contraception program in rural parts of the state in October.

Rural areas have disproportionately fewer doctors, including ob.gyns., than urban areas. And rural providers may not be able to afford to stock long-acting birth control devices or may not be trained in administering them, program leaders say.

Mobile clinics help shrink that gap in rural care, but they can be challenging to operate, said Elizabeth Jones, a senior director at the National Family Planning & Reproductive Health Association.

Money is the greatest obstacle, Jones said. The Texas program costs up to $400,000 a year. A 2020 study of 173 mobile clinics found they cost an average of more than $630,000 a year. Mobile dental programs were the most expensive, averaging more than $1 million.

While many programs launch with the help of grants, they can be difficult to sustain, especially with over a decade of decreased or stagnant funding to Title X, a federal money stream that helps low-income people receive family planning services.

For example, a mobile contraception program serving rural Pennsylvania lasted less than 3 years before closing in 2023. It shut down after losing federal funding, said a spokesperson for the clinic that ran it.

Rural mobile programs aren’t as efficient or profitable as brick-and-mortar clinics. That’s because staff members may have to make hours-long trips to reach towns where they’ll probably see fewer patients than they would at a traditional site, Jones said.

She said organizations that can’t afford mobile programs can consider setting up “pop-up clinics” at existing health and community sites in rural areas.

Maria Briones is a patient who has benefited from the Healthy Mujeres program in southern Texas. The 41-year-old day care worker was concerned because she wasn’t getting her menstrual period with her IUD.

She considered going to Mexico to have the device removed because few doctors take her insurance on the US side of the Rio Grande Valley.

But Briones learned that the UniMóvil was visiting a small Texas city about 20 minutes from her home. She told the staff there that she doesn’t want more kids but was worried about the IUD.

Briones decided to keep the device after learning it’s safe and normal not to have periods while using an IUD. She won’t get billed for her appointment with the mobile clinic, even though the university health system doesn’t take her insurance.

“They have a lot of patience, and they answered all the questions that I had,” Briones said.

IUDs and hormonal implants are highly effective and can last up to 10 years. But they’re also expensive — devices can cost more than $1,000 without insurance — and inserting an IUD can be painful.

Patient-rights advocates are also concerned that some providers pressure people to use these devices.

They say ethical birth control programs aim to empower patients to choose the contraceptive method — if any — that is best for them, instead of promoting long-acting methods in an attempt to lower birth and poverty rates. They point to the history of eugenics-inspired sterilization and even more recent incidents.

For example, an investigation by Time magazine found doctors are more likely to push Black, Latina, young, and low-income women than other patients to use long-acting birth control — and to refuse to remove the devices.

Rivas said Healthy Mujeres staffers are trained on this issue.

“Our goal isn’t necessarily to place IUDs and implants,” he said. It’s to “provide education and help patients make the best decisions for themselves.”

David Wise, a spokesperson for the University of Arkansas for Medical Sciences, said staff members with the university’s mobile program will ask patients if they want to get pregnant in the next year, and will support their choice. The Arkansas and Texas programs also remove IUDs and hormonal arm implants if patients aren’t happy with them.

The Arkansas initiative will visit 14 rural counties with four vehicles the size of food trucks that were used in previous mobile health efforts. Staffing and equipment will be covered by a 2-year, $431,000 grant from an anonymous donor, Wise said.

In addition to contraception, faculty and medical residents staffing the vehicles will offer women’s health screenings, vaccinations, prenatal care, and testing and treatment for sexually transmitted infections.

Rivas said the Texas program was inspired by a study that found that, 6 months after giving birth, 34% of surveyed Texas mothers said long-acting contraception is their preferred birth control option — but only 13% were using that method.

“We started thinking about ways to address that gap,” Rivas said.

Healthy Mujeres, which is funded through multiple grants, started with a focus on contraception. It later expanded to services such as pregnancy ultrasounds, cervical cancer screenings, and testing for sexually transmitted infections.

While the Texas and Arkansas programs can bill insurance, they also have funding to help uninsured and underinsured patients afford their services. Both use community health workers — called promotoras in largely Spanish-speaking communities like the Rio Grande Valley — to connect patients with food, transportation, additional medical services, and other needs.

They partner with organizations that locals trust, such as food pantries and community colleges, which let the mobile units set up in their parking lots. And to further increase the availability of long-acting contraception in rural areas, the universities are training their students and local providers on how to insert, remove, and get reimbursed for the devices.

One difference between the programs is dictated by state laws. The Arkansas program can provide birth control to minors without a parent or guardian’s consent. But in Texas, most minors need consent before receiving health care, including contraception.

Advocates say these initiatives might help lower the rates of unintended and teen pregnancies in both states, which are higher than the national average.

Rivas and Conroy said their programs haven’t received much pushback. But Rivas said some churches that had asked the UniMóvil to visit their congregations changed their minds after learning the services included birth control.

Catherine Phillips, director of the Respect Life Office at Arkansas’ Catholic diocese, said the diocese supports efforts to achieve health care equity and she’s personally interested in mobile programs that visit rural areas such as where she lives.

But Phillips said the Arkansas program’s focus on birth control, especially long-acting methods, violates the teachings of the Catholic Church. Offering these services to minors without parental consent “makes it more egregious,” she said.

Jones said that, while these programs have hefty costs and other challenges, they also have benefits that can’t be measured in numbers.

“Building community trust and making an impact in the communities most impacted by health inequities — that’s invaluable,” she said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Twice a month, a 40-foot-long truck transformed into a mobile clinic travels the Rio Grande Valley to provide rural Texans with women’s health care, including birth control.

The clinic, called the UniMóvil, is part of the Healthy Mujeres program at the University of Texas Rio Grande Valley School of Medicine in Edinburg.

The United States has about 3000 mobile health programs. But Saul Rivas, an ob.gyn., said he wasn’t aware of any that shared the specific mission of Healthy Mujeres when he helped launch the initiative in 2017. “Mujeres” means “women” in Spanish.

It’s now part of a small but growing number of mobile programs aimed at increasing rural access to women’s health services, including long-acting reversible contraception.

There are two kinds of these highly effective methods: intrauterine devices, known as IUDs, and hormonal implants inserted into the upper arm. These birth control options can be especially difficult to obtain — or have removed — in rural areas.

“Women who want to prevent an unintended pregnancy should have whatever works best for them,” said Kelly Conroy, senior director of mobile and maternal health programs at the University of Arkansas for Medical Sciences, Little Rock.

The school is launching a mobile women’s health and contraception program in rural parts of the state in October.

Rural areas have disproportionately fewer doctors, including ob.gyns., than urban areas. And rural providers may not be able to afford to stock long-acting birth control devices or may not be trained in administering them, program leaders say.

Mobile clinics help shrink that gap in rural care, but they can be challenging to operate, said Elizabeth Jones, a senior director at the National Family Planning & Reproductive Health Association.

Money is the greatest obstacle, Jones said. The Texas program costs up to $400,000 a year. A 2020 study of 173 mobile clinics found they cost an average of more than $630,000 a year. Mobile dental programs were the most expensive, averaging more than $1 million.

While many programs launch with the help of grants, they can be difficult to sustain, especially with over a decade of decreased or stagnant funding to Title X, a federal money stream that helps low-income people receive family planning services.

For example, a mobile contraception program serving rural Pennsylvania lasted less than 3 years before closing in 2023. It shut down after losing federal funding, said a spokesperson for the clinic that ran it.

Rural mobile programs aren’t as efficient or profitable as brick-and-mortar clinics. That’s because staff members may have to make hours-long trips to reach towns where they’ll probably see fewer patients than they would at a traditional site, Jones said.

She said organizations that can’t afford mobile programs can consider setting up “pop-up clinics” at existing health and community sites in rural areas.

Maria Briones is a patient who has benefited from the Healthy Mujeres program in southern Texas. The 41-year-old day care worker was concerned because she wasn’t getting her menstrual period with her IUD.

She considered going to Mexico to have the device removed because few doctors take her insurance on the US side of the Rio Grande Valley.

But Briones learned that the UniMóvil was visiting a small Texas city about 20 minutes from her home. She told the staff there that she doesn’t want more kids but was worried about the IUD.

Briones decided to keep the device after learning it’s safe and normal not to have periods while using an IUD. She won’t get billed for her appointment with the mobile clinic, even though the university health system doesn’t take her insurance.

“They have a lot of patience, and they answered all the questions that I had,” Briones said.

IUDs and hormonal implants are highly effective and can last up to 10 years. But they’re also expensive — devices can cost more than $1,000 without insurance — and inserting an IUD can be painful.

Patient-rights advocates are also concerned that some providers pressure people to use these devices.

They say ethical birth control programs aim to empower patients to choose the contraceptive method — if any — that is best for them, instead of promoting long-acting methods in an attempt to lower birth and poverty rates. They point to the history of eugenics-inspired sterilization and even more recent incidents.

For example, an investigation by Time magazine found doctors are more likely to push Black, Latina, young, and low-income women than other patients to use long-acting birth control — and to refuse to remove the devices.

Rivas said Healthy Mujeres staffers are trained on this issue.

“Our goal isn’t necessarily to place IUDs and implants,” he said. It’s to “provide education and help patients make the best decisions for themselves.”

David Wise, a spokesperson for the University of Arkansas for Medical Sciences, said staff members with the university’s mobile program will ask patients if they want to get pregnant in the next year, and will support their choice. The Arkansas and Texas programs also remove IUDs and hormonal arm implants if patients aren’t happy with them.

The Arkansas initiative will visit 14 rural counties with four vehicles the size of food trucks that were used in previous mobile health efforts. Staffing and equipment will be covered by a 2-year, $431,000 grant from an anonymous donor, Wise said.

In addition to contraception, faculty and medical residents staffing the vehicles will offer women’s health screenings, vaccinations, prenatal care, and testing and treatment for sexually transmitted infections.

Rivas said the Texas program was inspired by a study that found that, 6 months after giving birth, 34% of surveyed Texas mothers said long-acting contraception is their preferred birth control option — but only 13% were using that method.

“We started thinking about ways to address that gap,” Rivas said.

Healthy Mujeres, which is funded through multiple grants, started with a focus on contraception. It later expanded to services such as pregnancy ultrasounds, cervical cancer screenings, and testing for sexually transmitted infections.

While the Texas and Arkansas programs can bill insurance, they also have funding to help uninsured and underinsured patients afford their services. Both use community health workers — called promotoras in largely Spanish-speaking communities like the Rio Grande Valley — to connect patients with food, transportation, additional medical services, and other needs.

They partner with organizations that locals trust, such as food pantries and community colleges, which let the mobile units set up in their parking lots. And to further increase the availability of long-acting contraception in rural areas, the universities are training their students and local providers on how to insert, remove, and get reimbursed for the devices.

One difference between the programs is dictated by state laws. The Arkansas program can provide birth control to minors without a parent or guardian’s consent. But in Texas, most minors need consent before receiving health care, including contraception.

Advocates say these initiatives might help lower the rates of unintended and teen pregnancies in both states, which are higher than the national average.

Rivas and Conroy said their programs haven’t received much pushback. But Rivas said some churches that had asked the UniMóvil to visit their congregations changed their minds after learning the services included birth control.

Catherine Phillips, director of the Respect Life Office at Arkansas’ Catholic diocese, said the diocese supports efforts to achieve health care equity and she’s personally interested in mobile programs that visit rural areas such as where she lives.

But Phillips said the Arkansas program’s focus on birth control, especially long-acting methods, violates the teachings of the Catholic Church. Offering these services to minors without parental consent “makes it more egregious,” she said.

Jones said that, while these programs have hefty costs and other challenges, they also have benefits that can’t be measured in numbers.

“Building community trust and making an impact in the communities most impacted by health inequities — that’s invaluable,” she said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Premenstrual disorders (PMDs), including premenstrual dysphoric disorder (PMDD), adversely affect the lives of millions of women worldwide. Most girls and women — as many as 80%-90%— will experience some premenstrual discomfort such as irritability, depressed mood, food or alcohol cravings, bloating, body aches, breast pain, constipation, or fatigue.

Diagnosable menstrual disorders include, collectively, premenstrual syndrome (PMS); PMDD, formerly called late luteal phase dysphoric disorder; and premenstrual worsening of another medical condition.

The most debilitating of these is PMDD, which has an estimated prevalence of about 4%-8% in women of reproductive age, according to obstetrician/gynecologist Hoosna Haque, MD, assistant professor of medicine at Columbia University Irving Medical Center in New York City.

“It’s difficult to be sure because this condition is underreported,” said Luu D. Ireland, MD, MPH, assistant professor of obstetrics and gynecology at UMass Memorial Medical Center in Worcester, Massachusetts. “But more women are coming forward, and there’s more discussion and media coverage of this condition.”

Occurring in the same post-follicular timeframe as PMS, PMDD takes cyclical discomfort to a more intense level, with a trifecta of affective comorbidities, somatic manifestations, and behavioral changes, all of which can seriously impair daily functioning, including work, physical activities, and personal relationships. Romantic and marital relationships can be particularly impaired.

Although recent cost figures are lacking, PMDs exact a considerable economic toll with increased direct healthcare costs from doctor visits and pharmaceuticals. A 2010 study found that US women with PMS were more likely to accrue in excess of $500 in healthcare visit costs over 2 years, and the figure would likely be higher today. PMDs also increase work/school absenteeism and reduce productivity.
 

Etiology

Brain areas that regulate emotion and behavior contain receptors for estrogen, progesterone, and other sex hormones, which affect the functioning of neurotransmitter systems influencing mood and thinking. Although the precise pathophysiology remains unclear, PMDD is likely multifactorial and results in a heightened sensitivity to normal fluctuations in estrogen and progesterone during the luteal phase of the menstrual cycle and dysfunction of the serotonin and gamma-aminobutyric acid neurotransmitter systems.

Patients with PMDD have lower levels of cortisol and beta-endorphins during both the follicular and luteal phases, suggesting abnormalities in the hypothalamic-pituitary-gonadal axis (HPGA), which is consistent with dysregulation in mood disorders.
 

Risk Factors

These include family history, past traumatic events, smoking, chronic pain syndrome, and obesity. There may be a genetic component as recent studies have suggested the involvement of the gene that codes for the serotonergic 5HT1A receptor and allelic variants of ESR1 in the development of PMS/PMDD.

A particularly concerning aspect of PMDs of any sort is their possible association with a higher risk for death from non-natural causes. In a recent Swedish study, which did not distinguish between PMDs in general and PMDD in particular, patients had an almost 60% greater risk for death from non-natural causes and nearly twice the risk for death by suicide compared with women without PMDs.

Those diagnosed with a PMD at an early age showed excess mortality, and the risk for suicide was elevated regardless of age. “These findings support the need for careful follow-up for young women with PMDs and the need for suicide prevention strategies,” wrote lead author Marion Opatowski, PhD, a medical epidemiologist at Karolinska Institutet in Stockholm, Sweden. “Women with severe PMDD should definitely be monitored for suicidal thoughts or behavior and they should have an emergency outreach plan in place,” Haque added.
 

Diagnosis

Although the somatic manifestations of PMDD resemble those of PMS, they are more severe and associated psychological symptoms are greater. “In my experience, PMDD symptoms can last the whole 2 weeks of the luteal phase, whereas PMS might occur a couple of days before menstruation,” said Ireland.

Symptoms include labile mood, nervousness, hopelessness, anger and aggressiveness, as well as tension and irritability. Those affected may have suicidal thoughts or even behaviors. In addition to a lethargic loss of interest in normal activities, patients with PMDD may feel paranoid, confused, exhausted, or out of control and experience insomnia or hypersomnia. They may have trouble concentrating or remembering. Some patients with PMDD may already be prone to attention-deficit/hyperactivity disorder and non–cycle-related depression, anxiety, and panic attacks.

Diagnosis is based on the presence of any five of the typical affective, somatic, or behavioral symptoms outlined above in the week before onset of menses.

“It’s important to do a careful diagnosis for PMDD and rule out other underlying conditions such as existing depressive or anxiety disorders,” said Haque. “Symptoms tend to be more intense in periods of high hormonal fluctuation such as in the postpartum and perimenopause periods. Women with PMDD should be monitored for postpartum depression.”

PMDD is considered both a gynecologic-genitourinary disorder and an affective condition.

In 2013, it was controversially included as a depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Strongly advocated by some patients, psychiatrists, and pharmaceutical companies, its inclusion was criticized by psychologists and generalists, who feared it would lead to overdiagnosis and pathologization of normal female hormonal changes. Women’s advocates protested that this inclusion would stigmatize female biology and harm their advance in society and the workplace, while some doctors continued to dismiss PMDD as not a serious concern.
 

Treatments

In its latest clinical practice guideline on PMDs, the American College of Obstetricians and Gynecologists (ACOG), for which Ireland served as the lead author, recommends that most patients with PMDD get medical treatment and outlines the following therapies, based on varying degrees of evidence strength.

Antidepressants. These may benefit patients with strong affective symptoms. Selective serotonin reuptake inhibitors such as sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), or fluoxetine (Prozac) are first choices.

Antidepressants may interrupt aberrant signaling in the HPGA, the circuit linking brain and ovaries and regulating the reproductive cycle. Serotonin norepinephrine reuptake inhibitor venlafaxine (Effexor) may also improve symptoms, but other types of antidepressants have not proven effective.

“The response to these well-tolerated drugs is rapid and can happen in the first 2 days,” said Ireland. The drugs may be taken either just in the luteal period or over the month, especially by patients with chronic depression or anxiety.

Hormonal therapy. ACOG recommends the use of combined oral contraceptives (COCs), gonadotropin-releasing hormone (GnRH) agonists to induce anovulation (with combined add-back hormones), progestin-only methods, and noncontraceptive continuous estrogen formulations. It notes, however, that COCs have not been more effective than placebo in reducing depressive symptom scores.

If symptoms do not improve over two to three cycles, an alternate therapy should be considered. Haque recommends an assessment after three cycles and then yearly.

Some women in her practice take both antidepressant and hormone therapy. “Unfortunately, there are no new pharmaceutical treatments on the horizon, but we have good ones already and we would love for patients to utilize them more often,” Ireland said.

Nonsteroidal anti-inflammatory drugs. Limited evidence shows these may reduce physical symptoms such as abdominal cramps, headaches, and general body aches, as well as some mood-related symptoms, which may be an indirect effect of pain alleviation.

Surgery. For women with the most severe intractable symptoms, bilateral oophorectomy with or without hysterectomy may be a last-resort option when medical management has failed. A trial period of GnRH agonist therapy (with or without adjunctive estrogen add-back treatment) is advised before surgery to predict a patient’s response to surgical management.

Acupuncture. ACOG suggests that acupuncture may help manage physical and affective premenstrual symptoms.

Diet. The usual dietary advice for premenstrual symptoms — such as consuming less caffeine, sugar, or alcohol and eating smaller, more frequent meals — is unlikely to help women with PMDD.

Exercise. Although it has not been well studied for PMDD, aerobic exercises such as walking, swimming, and biking tend to improve mood and energy levels in general. Exercise may reduce symptoms through several pathways, including effects on beta-endorphin, cortisol, and ovarian hormone levels.

Supplements. Vitamin B6, calcium and magnesium supplements, and herbal remedies are not supported by consistent or compelling evidence of efficacy. ACOG conditionally recommends calcium supplementation of 100-200 mg/d in adults to help manage physical and affective symptoms.

A small study suggested that supplemental zinc may improve both physical and psychological symptoms.

Cognitive-behavioral therapy. This treatment aims to interrupt negative and irrational thought patterns and may include awareness and education, as well as relaxation techniques, problem-solving and coping skills, and stress management. It has been associated with small to moderate improvement in anxiety and depression, said Ireland.

Peer support. Patients should consider joining a support group. The International Association for Premenstrual Disorders can help patients connect and develop coping skills.

The bottom line is that people with strong symptomatic evidence of PMDD should have medical intervention — to the benefit of their health and quality of life. Screening for PMDD should be part of women’s wellness examinations, said Ireland. “The impact of PMDD should not be minimized or dismissed,” said Haque. “And patients need to know there are very effective treatments.”

Ireland and Haque had no competing interests with regard to their comments.
 

A version of this article first appeared on Medscape.com.

Premenstrual disorders (PMDs), including premenstrual dysphoric disorder (PMDD), adversely affect the lives of millions of women worldwide. Most girls and women — as many as 80%-90%— will experience some premenstrual discomfort such as irritability, depressed mood, food or alcohol cravings, bloating, body aches, breast pain, constipation, or fatigue.

Diagnosable menstrual disorders include, collectively, premenstrual syndrome (PMS); PMDD, formerly called late luteal phase dysphoric disorder; and premenstrual worsening of another medical condition.

The most debilitating of these is PMDD, which has an estimated prevalence of about 4%-8% in women of reproductive age, according to obstetrician/gynecologist Hoosna Haque, MD, assistant professor of medicine at Columbia University Irving Medical Center in New York City.

“It’s difficult to be sure because this condition is underreported,” said Luu D. Ireland, MD, MPH, assistant professor of obstetrics and gynecology at UMass Memorial Medical Center in Worcester, Massachusetts. “But more women are coming forward, and there’s more discussion and media coverage of this condition.”

Occurring in the same post-follicular timeframe as PMS, PMDD takes cyclical discomfort to a more intense level, with a trifecta of affective comorbidities, somatic manifestations, and behavioral changes, all of which can seriously impair daily functioning, including work, physical activities, and personal relationships. Romantic and marital relationships can be particularly impaired.

Although recent cost figures are lacking, PMDs exact a considerable economic toll with increased direct healthcare costs from doctor visits and pharmaceuticals. A 2010 study found that US women with PMS were more likely to accrue in excess of $500 in healthcare visit costs over 2 years, and the figure would likely be higher today. PMDs also increase work/school absenteeism and reduce productivity.
 

Etiology

Brain areas that regulate emotion and behavior contain receptors for estrogen, progesterone, and other sex hormones, which affect the functioning of neurotransmitter systems influencing mood and thinking. Although the precise pathophysiology remains unclear, PMDD is likely multifactorial and results in a heightened sensitivity to normal fluctuations in estrogen and progesterone during the luteal phase of the menstrual cycle and dysfunction of the serotonin and gamma-aminobutyric acid neurotransmitter systems.

Patients with PMDD have lower levels of cortisol and beta-endorphins during both the follicular and luteal phases, suggesting abnormalities in the hypothalamic-pituitary-gonadal axis (HPGA), which is consistent with dysregulation in mood disorders.
 

Risk Factors

These include family history, past traumatic events, smoking, chronic pain syndrome, and obesity. There may be a genetic component as recent studies have suggested the involvement of the gene that codes for the serotonergic 5HT1A receptor and allelic variants of ESR1 in the development of PMS/PMDD.

A particularly concerning aspect of PMDs of any sort is their possible association with a higher risk for death from non-natural causes. In a recent Swedish study, which did not distinguish between PMDs in general and PMDD in particular, patients had an almost 60% greater risk for death from non-natural causes and nearly twice the risk for death by suicide compared with women without PMDs.

Those diagnosed with a PMD at an early age showed excess mortality, and the risk for suicide was elevated regardless of age. “These findings support the need for careful follow-up for young women with PMDs and the need for suicide prevention strategies,” wrote lead author Marion Opatowski, PhD, a medical epidemiologist at Karolinska Institutet in Stockholm, Sweden. “Women with severe PMDD should definitely be monitored for suicidal thoughts or behavior and they should have an emergency outreach plan in place,” Haque added.
 

Diagnosis

Although the somatic manifestations of PMDD resemble those of PMS, they are more severe and associated psychological symptoms are greater. “In my experience, PMDD symptoms can last the whole 2 weeks of the luteal phase, whereas PMS might occur a couple of days before menstruation,” said Ireland.

Symptoms include labile mood, nervousness, hopelessness, anger and aggressiveness, as well as tension and irritability. Those affected may have suicidal thoughts or even behaviors. In addition to a lethargic loss of interest in normal activities, patients with PMDD may feel paranoid, confused, exhausted, or out of control and experience insomnia or hypersomnia. They may have trouble concentrating or remembering. Some patients with PMDD may already be prone to attention-deficit/hyperactivity disorder and non–cycle-related depression, anxiety, and panic attacks.

Diagnosis is based on the presence of any five of the typical affective, somatic, or behavioral symptoms outlined above in the week before onset of menses.

“It’s important to do a careful diagnosis for PMDD and rule out other underlying conditions such as existing depressive or anxiety disorders,” said Haque. “Symptoms tend to be more intense in periods of high hormonal fluctuation such as in the postpartum and perimenopause periods. Women with PMDD should be monitored for postpartum depression.”

PMDD is considered both a gynecologic-genitourinary disorder and an affective condition.

In 2013, it was controversially included as a depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Strongly advocated by some patients, psychiatrists, and pharmaceutical companies, its inclusion was criticized by psychologists and generalists, who feared it would lead to overdiagnosis and pathologization of normal female hormonal changes. Women’s advocates protested that this inclusion would stigmatize female biology and harm their advance in society and the workplace, while some doctors continued to dismiss PMDD as not a serious concern.
 

Treatments

In its latest clinical practice guideline on PMDs, the American College of Obstetricians and Gynecologists (ACOG), for which Ireland served as the lead author, recommends that most patients with PMDD get medical treatment and outlines the following therapies, based on varying degrees of evidence strength.

Antidepressants. These may benefit patients with strong affective symptoms. Selective serotonin reuptake inhibitors such as sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), or fluoxetine (Prozac) are first choices.

Antidepressants may interrupt aberrant signaling in the HPGA, the circuit linking brain and ovaries and regulating the reproductive cycle. Serotonin norepinephrine reuptake inhibitor venlafaxine (Effexor) may also improve symptoms, but other types of antidepressants have not proven effective.

“The response to these well-tolerated drugs is rapid and can happen in the first 2 days,” said Ireland. The drugs may be taken either just in the luteal period or over the month, especially by patients with chronic depression or anxiety.

Hormonal therapy. ACOG recommends the use of combined oral contraceptives (COCs), gonadotropin-releasing hormone (GnRH) agonists to induce anovulation (with combined add-back hormones), progestin-only methods, and noncontraceptive continuous estrogen formulations. It notes, however, that COCs have not been more effective than placebo in reducing depressive symptom scores.

If symptoms do not improve over two to three cycles, an alternate therapy should be considered. Haque recommends an assessment after three cycles and then yearly.

Some women in her practice take both antidepressant and hormone therapy. “Unfortunately, there are no new pharmaceutical treatments on the horizon, but we have good ones already and we would love for patients to utilize them more often,” Ireland said.

Nonsteroidal anti-inflammatory drugs. Limited evidence shows these may reduce physical symptoms such as abdominal cramps, headaches, and general body aches, as well as some mood-related symptoms, which may be an indirect effect of pain alleviation.

Surgery. For women with the most severe intractable symptoms, bilateral oophorectomy with or without hysterectomy may be a last-resort option when medical management has failed. A trial period of GnRH agonist therapy (with or without adjunctive estrogen add-back treatment) is advised before surgery to predict a patient’s response to surgical management.

Acupuncture. ACOG suggests that acupuncture may help manage physical and affective premenstrual symptoms.

Diet. The usual dietary advice for premenstrual symptoms — such as consuming less caffeine, sugar, or alcohol and eating smaller, more frequent meals — is unlikely to help women with PMDD.

Exercise. Although it has not been well studied for PMDD, aerobic exercises such as walking, swimming, and biking tend to improve mood and energy levels in general. Exercise may reduce symptoms through several pathways, including effects on beta-endorphin, cortisol, and ovarian hormone levels.

Supplements. Vitamin B6, calcium and magnesium supplements, and herbal remedies are not supported by consistent or compelling evidence of efficacy. ACOG conditionally recommends calcium supplementation of 100-200 mg/d in adults to help manage physical and affective symptoms.

A small study suggested that supplemental zinc may improve both physical and psychological symptoms.

Cognitive-behavioral therapy. This treatment aims to interrupt negative and irrational thought patterns and may include awareness and education, as well as relaxation techniques, problem-solving and coping skills, and stress management. It has been associated with small to moderate improvement in anxiety and depression, said Ireland.

Peer support. Patients should consider joining a support group. The International Association for Premenstrual Disorders can help patients connect and develop coping skills.

The bottom line is that people with strong symptomatic evidence of PMDD should have medical intervention — to the benefit of their health and quality of life. Screening for PMDD should be part of women’s wellness examinations, said Ireland. “The impact of PMDD should not be minimized or dismissed,” said Haque. “And patients need to know there are very effective treatments.”

Ireland and Haque had no competing interests with regard to their comments.
 

A version of this article first appeared on Medscape.com.

Premenstrual disorders (PMDs), including premenstrual dysphoric disorder (PMDD), adversely affect the lives of millions of women worldwide. Most girls and women — as many as 80%-90%— will experience some premenstrual discomfort such as irritability, depressed mood, food or alcohol cravings, bloating, body aches, breast pain, constipation, or fatigue.

Diagnosable menstrual disorders include, collectively, premenstrual syndrome (PMS); PMDD, formerly called late luteal phase dysphoric disorder; and premenstrual worsening of another medical condition.

The most debilitating of these is PMDD, which has an estimated prevalence of about 4%-8% in women of reproductive age, according to obstetrician/gynecologist Hoosna Haque, MD, assistant professor of medicine at Columbia University Irving Medical Center in New York City.

“It’s difficult to be sure because this condition is underreported,” said Luu D. Ireland, MD, MPH, assistant professor of obstetrics and gynecology at UMass Memorial Medical Center in Worcester, Massachusetts. “But more women are coming forward, and there’s more discussion and media coverage of this condition.”

Occurring in the same post-follicular timeframe as PMS, PMDD takes cyclical discomfort to a more intense level, with a trifecta of affective comorbidities, somatic manifestations, and behavioral changes, all of which can seriously impair daily functioning, including work, physical activities, and personal relationships. Romantic and marital relationships can be particularly impaired.

Although recent cost figures are lacking, PMDs exact a considerable economic toll with increased direct healthcare costs from doctor visits and pharmaceuticals. A 2010 study found that US women with PMS were more likely to accrue in excess of $500 in healthcare visit costs over 2 years, and the figure would likely be higher today. PMDs also increase work/school absenteeism and reduce productivity.
 

Etiology

Brain areas that regulate emotion and behavior contain receptors for estrogen, progesterone, and other sex hormones, which affect the functioning of neurotransmitter systems influencing mood and thinking. Although the precise pathophysiology remains unclear, PMDD is likely multifactorial and results in a heightened sensitivity to normal fluctuations in estrogen and progesterone during the luteal phase of the menstrual cycle and dysfunction of the serotonin and gamma-aminobutyric acid neurotransmitter systems.

Patients with PMDD have lower levels of cortisol and beta-endorphins during both the follicular and luteal phases, suggesting abnormalities in the hypothalamic-pituitary-gonadal axis (HPGA), which is consistent with dysregulation in mood disorders.
 

Risk Factors

These include family history, past traumatic events, smoking, chronic pain syndrome, and obesity. There may be a genetic component as recent studies have suggested the involvement of the gene that codes for the serotonergic 5HT1A receptor and allelic variants of ESR1 in the development of PMS/PMDD.

A particularly concerning aspect of PMDs of any sort is their possible association with a higher risk for death from non-natural causes. In a recent Swedish study, which did not distinguish between PMDs in general and PMDD in particular, patients had an almost 60% greater risk for death from non-natural causes and nearly twice the risk for death by suicide compared with women without PMDs.

Those diagnosed with a PMD at an early age showed excess mortality, and the risk for suicide was elevated regardless of age. “These findings support the need for careful follow-up for young women with PMDs and the need for suicide prevention strategies,” wrote lead author Marion Opatowski, PhD, a medical epidemiologist at Karolinska Institutet in Stockholm, Sweden. “Women with severe PMDD should definitely be monitored for suicidal thoughts or behavior and they should have an emergency outreach plan in place,” Haque added.
 

Diagnosis

Although the somatic manifestations of PMDD resemble those of PMS, they are more severe and associated psychological symptoms are greater. “In my experience, PMDD symptoms can last the whole 2 weeks of the luteal phase, whereas PMS might occur a couple of days before menstruation,” said Ireland.

Symptoms include labile mood, nervousness, hopelessness, anger and aggressiveness, as well as tension and irritability. Those affected may have suicidal thoughts or even behaviors. In addition to a lethargic loss of interest in normal activities, patients with PMDD may feel paranoid, confused, exhausted, or out of control and experience insomnia or hypersomnia. They may have trouble concentrating or remembering. Some patients with PMDD may already be prone to attention-deficit/hyperactivity disorder and non–cycle-related depression, anxiety, and panic attacks.

Diagnosis is based on the presence of any five of the typical affective, somatic, or behavioral symptoms outlined above in the week before onset of menses.

“It’s important to do a careful diagnosis for PMDD and rule out other underlying conditions such as existing depressive or anxiety disorders,” said Haque. “Symptoms tend to be more intense in periods of high hormonal fluctuation such as in the postpartum and perimenopause periods. Women with PMDD should be monitored for postpartum depression.”

PMDD is considered both a gynecologic-genitourinary disorder and an affective condition.

In 2013, it was controversially included as a depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Strongly advocated by some patients, psychiatrists, and pharmaceutical companies, its inclusion was criticized by psychologists and generalists, who feared it would lead to overdiagnosis and pathologization of normal female hormonal changes. Women’s advocates protested that this inclusion would stigmatize female biology and harm their advance in society and the workplace, while some doctors continued to dismiss PMDD as not a serious concern.
 

Treatments

In its latest clinical practice guideline on PMDs, the American College of Obstetricians and Gynecologists (ACOG), for which Ireland served as the lead author, recommends that most patients with PMDD get medical treatment and outlines the following therapies, based on varying degrees of evidence strength.

Antidepressants. These may benefit patients with strong affective symptoms. Selective serotonin reuptake inhibitors such as sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), or fluoxetine (Prozac) are first choices.

Antidepressants may interrupt aberrant signaling in the HPGA, the circuit linking brain and ovaries and regulating the reproductive cycle. Serotonin norepinephrine reuptake inhibitor venlafaxine (Effexor) may also improve symptoms, but other types of antidepressants have not proven effective.

“The response to these well-tolerated drugs is rapid and can happen in the first 2 days,” said Ireland. The drugs may be taken either just in the luteal period or over the month, especially by patients with chronic depression or anxiety.

Hormonal therapy. ACOG recommends the use of combined oral contraceptives (COCs), gonadotropin-releasing hormone (GnRH) agonists to induce anovulation (with combined add-back hormones), progestin-only methods, and noncontraceptive continuous estrogen formulations. It notes, however, that COCs have not been more effective than placebo in reducing depressive symptom scores.

If symptoms do not improve over two to three cycles, an alternate therapy should be considered. Haque recommends an assessment after three cycles and then yearly.

Some women in her practice take both antidepressant and hormone therapy. “Unfortunately, there are no new pharmaceutical treatments on the horizon, but we have good ones already and we would love for patients to utilize them more often,” Ireland said.

Nonsteroidal anti-inflammatory drugs. Limited evidence shows these may reduce physical symptoms such as abdominal cramps, headaches, and general body aches, as well as some mood-related symptoms, which may be an indirect effect of pain alleviation.

Surgery. For women with the most severe intractable symptoms, bilateral oophorectomy with or without hysterectomy may be a last-resort option when medical management has failed. A trial period of GnRH agonist therapy (with or without adjunctive estrogen add-back treatment) is advised before surgery to predict a patient’s response to surgical management.

Acupuncture. ACOG suggests that acupuncture may help manage physical and affective premenstrual symptoms.

Diet. The usual dietary advice for premenstrual symptoms — such as consuming less caffeine, sugar, or alcohol and eating smaller, more frequent meals — is unlikely to help women with PMDD.

Exercise. Although it has not been well studied for PMDD, aerobic exercises such as walking, swimming, and biking tend to improve mood and energy levels in general. Exercise may reduce symptoms through several pathways, including effects on beta-endorphin, cortisol, and ovarian hormone levels.

Supplements. Vitamin B6, calcium and magnesium supplements, and herbal remedies are not supported by consistent or compelling evidence of efficacy. ACOG conditionally recommends calcium supplementation of 100-200 mg/d in adults to help manage physical and affective symptoms.

A small study suggested that supplemental zinc may improve both physical and psychological symptoms.

Cognitive-behavioral therapy. This treatment aims to interrupt negative and irrational thought patterns and may include awareness and education, as well as relaxation techniques, problem-solving and coping skills, and stress management. It has been associated with small to moderate improvement in anxiety and depression, said Ireland.

Peer support. Patients should consider joining a support group. The International Association for Premenstrual Disorders can help patients connect and develop coping skills.

The bottom line is that people with strong symptomatic evidence of PMDD should have medical intervention — to the benefit of their health and quality of life. Screening for PMDD should be part of women’s wellness examinations, said Ireland. “The impact of PMDD should not be minimized or dismissed,” said Haque. “And patients need to know there are very effective treatments.”

Ireland and Haque had no competing interests with regard to their comments.
 

A version of this article first appeared on Medscape.com.

It has been 24 years since a pharmaceutical was last approved for posttraumatic stress disorder (PTSD). The condition is notoriously difficult to treat, with up to 40% patients finding no relief from symptoms through psychotherapy or current medications.

Many clinicians, advocates, and patients had pinned their hopes on the psychedelic drug midomafetamine with assisted therapy (MDMA-AT). However, in August, the US Food and Drug Administration (FDA) rejected it. At this point, it’s unclear when the therapy will be available, if ever.

“Not getting the FDA approval of any drug at this point is a setback for the field,” Lori Davis, MD, a senior research psychiatrist at the Birmingham Veterans Affairs (VA) Health Care System in Birmingham, Alabama, told Medscape Medical News.

Having an FDA-approved product would have helped increase public awareness of PTSD and driven interest in developing new therapies, said Davis, who is also adjunct professor of psychiatry at the Heersink School of Medicine, University of Alabama at Birmingham.
 

A Treatable Condition

So with MDMA-AT off the table, where does the field go next? 

A public meeting in September hosted by the Reagan-Udall Foundation for the FDA in sought to answer that question. Agency officials joined representatives from the Department of Defense (DoD) and VA, patients, advocates, and industry representatives to discuss the current treatment landscape and what can be done to accelerate development of PTSD treatment.

Despite the common belief that PTSD is intractable, it “is a treatable condition,” Paula P. Schnurr, PhD, executive director of the VA National Center for PTSD, said at the meeting.

“There are effective treatments that work well for a lot of people, although not everyone has a satisfactory response,” she added.

The most effective psychotherapies are “trauma-focused,” and include cognitive processing therapy, eye movement desensitization and reprocessing, and prolonged exposure, according to the VA National Center for PTSD.

Three drugs have been approved by the FDA for PTSD: Venlafaxine (Effexor) in 1993, sertraline (Zoloft) in 1999, and paroxetine (Paxil) in 2000.

However, as the September meeting demonstrated, more therapies are needed.

“It’s clear to FDA and the federal government at large that there is an unmet need for safe and effective therapies to treat PTSD,” Bernard Fischer, MD, deputy director of the Division of Psychiatry in the Office of New Drugs at FDA’s Center for Drug Evaluation and Research, said at the meeting.

There is no shortage of research, Fischer added. Nearly 500 trials focused on PTSD are listed on clinicaltrials.gov are recruiting participants now or plan to soon.

Unsurprisingly, one of the primary drivers of PTSD therapeutics research is the VA. About 14% of the 5.7 million veterans who received care through the VA in 2023 had a diagnosis of PTSD.

“The US military is currently losing thousands of service members each year to PTSD- related disability discharges,” US Army Maj. Aaron Wolfgang, MD, a psychiatrist at the Walter Reed National Military Medical Center, said at the meeting. Only about 12%-20% of patients achieve remission with conventional therapies, added Wolfgang, who also is an assistant professor at the Uniformed Services University.

“For these reasons, establishing better treatments for PTSD is not only a matter of humanitarianism but also a pressing matter of national security,” he said.

The VA has committed at least $230 million to more than 140 active research projects in PTSD, Miriam J. Smyth, PhD, acting director of the clinical science, research and development service at the VA, said at the Reagan-Udall meeting.

One of the VA projects is the PTSD psychopharmacology initiative, which began in 2017 and now has 14 active clinical trials, said Smyth, who is also acting director for brain behavior and mental health at the VA. The first study should be finished by 2025.

The Million Veteran Program, with more than 1 million enrollees, has led to the discovery of genes related to re-experiencing traumatic memories and has confirmed that both PTSD and traumatic brain injury are risk factors for dementia, Smyth said.

The DoD has created a novel platform that establishes a common infrastructure for testing multiple drugs, called M-PACT. The platform allows sharing of placebo data across treatment arms. Drugs cycle off the platform if evidence indicates probability of success or failure.

Four trials are actively recruiting veterans and current service members. One is looking at vilazodone, approved in 2011 for major depressive disorder. It is being compared with placebo and fluoxetine in a trial that is currently recruiting.

Another trial will study daridorexant (sold as Quviviq), an orexin receptor antagonist, against placebo. The FDA approved daridorexant in 2022 as an insomnia treatment. A core issue in PTSD is sleep disruption, noted Davis.
 

New Therapies on the Way

Separately, Davis and colleagues are also studying methylphenidate, the stimulant used for attention-deficit/hyperactivity disorder. It may help with neurocognitive complaints and reduce PTSD symptoms, said Davis.

Because it is generic, few pharmaceutical manufacturers are likely to test it for PTSD, she said. But eventually, their work may lead a company to test newer stimulants for PTSD, she said.

Another potential therapeutic, BNC210, received Fast Track designation for PTSD from the FDA in 2019. Bionomics Limited in Australia will soon launch phase 3 trials of the investigational oral drug, which is a negative allosteric modulator of the alpha-7 nicotinic acetylcholine receptor. In late July, the company announced “ favorable feedback” from the agency on its phase 2 study, which led to the decision to move forward with larger trials.

Researchers at Brigham and Women’s Hospital have just reported that they may have found a target within the brain that will allow for transcranial magnetic stimulation (TMS) to ameliorate PTSD symptoms. They published results of a mapping effort in Nature Neuroscience and reported on one patient who had improved symptoms after receiving TMS for severe PTSD.

But perhaps one of the most promising treatments is a combination of sertraline and the new psychiatric medication brexpiprazole.

Brexpiprazole was developed by Otsuka Pharmaceutical and approved in the United States in 2015 as an adjunctive therapy to antidepressants for major depressive disorder and as a treatment for schizophrenia. In 2023, the FDA approved it for Alzheimer’s-related agitation. However, according to Otsuka, its mechanism of action is unknown.

Its efficacy may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, antagonist activity at serotonin 5-HT2A receptors, as well as antagonism of alpha-1B/2C receptors, said the company.

“It is the combination, rather than either alone, that’s going to have that broad synergistic pharmacology that is obviously potent for ameliorating the symptoms of PTSD,” said Davis, who has received consulting fees from Otsuka. “That’s an exciting development.”

Otsuka and partner Lundbeck Pharmaceuticals reported results in May from the companies’ phase 2 and 3 randomized clinical trials. The therapy achieved a statistically significant reduction (P <.05) in PTSD symptoms compared with sertraline plus placebo. This was without any supplemental psychotherapy.

The FDA accepted the companies’ new drug application in June and is expected to make a decision on approval in February 2025.
 

The Potential of Psychedelics

Though Lykos Therapeutics may have to go back to the drawing board on its MDMA-AT, psychedelics still have potential as PTSD therapies, Smyth said, who added that the VA is continuing to encourage study of MDMA and other psychedelic agents.

The VA issued a call for proposals for research on psychedelics in January, focused on MDMA or psilocybin in combination with psychotherapy. The administration received the first wave of applications early in the summer.

Scientific peer review panels made up of research experts from within and outside the VA have reviewed the applications and funding announcements are expected this fall, Smyth said.

Wolfgang, the Army psychiatrist, said, “Under the psychedelic treatment research clinical trial award, we welcome investigators to apply to what we anticipate will usher in a new era of innovation and hope for service members and their families who need it the most.”

Psychedelic studies are also proceeding without VA funding, as they have for years, when most of the trials were backed by universities or foundations or other private money. Johns Hopkins University is recruiting for a study in which patients would receive psilocybin along with trauma-focused psychotherapy, as is Ohio State University.

London-based Compass Pathways said in May that it successfully completed a phase 2 trial of Comp360, its synthetic psilocybin, in PTSD. The company has started a phase 3 study in treatment-resistant depression but has not given any further updates on PTSD.

Davis said that she believes that the FDA’s rejection of Lykos won’t lead to a shutdown of exploration of psychedelics.

“I think it informs these designs going forward, but it doesn’t eliminate that whole field of research,” she said.

Davis reported receiving consulting fees from Boehringer Ingelheim and Otsuka and research funding from Alkermes, the Patient-Centered Outcomes Research Institute, and the VA. Schnurr, Fischer, Smyth, and Wolfgang reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

It has been 24 years since a pharmaceutical was last approved for posttraumatic stress disorder (PTSD). The condition is notoriously difficult to treat, with up to 40% patients finding no relief from symptoms through psychotherapy or current medications.

Many clinicians, advocates, and patients had pinned their hopes on the psychedelic drug midomafetamine with assisted therapy (MDMA-AT). However, in August, the US Food and Drug Administration (FDA) rejected it. At this point, it’s unclear when the therapy will be available, if ever.

“Not getting the FDA approval of any drug at this point is a setback for the field,” Lori Davis, MD, a senior research psychiatrist at the Birmingham Veterans Affairs (VA) Health Care System in Birmingham, Alabama, told Medscape Medical News.

Having an FDA-approved product would have helped increase public awareness of PTSD and driven interest in developing new therapies, said Davis, who is also adjunct professor of psychiatry at the Heersink School of Medicine, University of Alabama at Birmingham.
 

A Treatable Condition

So with MDMA-AT off the table, where does the field go next? 

A public meeting in September hosted by the Reagan-Udall Foundation for the FDA in sought to answer that question. Agency officials joined representatives from the Department of Defense (DoD) and VA, patients, advocates, and industry representatives to discuss the current treatment landscape and what can be done to accelerate development of PTSD treatment.

Despite the common belief that PTSD is intractable, it “is a treatable condition,” Paula P. Schnurr, PhD, executive director of the VA National Center for PTSD, said at the meeting.

“There are effective treatments that work well for a lot of people, although not everyone has a satisfactory response,” she added.

The most effective psychotherapies are “trauma-focused,” and include cognitive processing therapy, eye movement desensitization and reprocessing, and prolonged exposure, according to the VA National Center for PTSD.

Three drugs have been approved by the FDA for PTSD: Venlafaxine (Effexor) in 1993, sertraline (Zoloft) in 1999, and paroxetine (Paxil) in 2000.

However, as the September meeting demonstrated, more therapies are needed.

“It’s clear to FDA and the federal government at large that there is an unmet need for safe and effective therapies to treat PTSD,” Bernard Fischer, MD, deputy director of the Division of Psychiatry in the Office of New Drugs at FDA’s Center for Drug Evaluation and Research, said at the meeting.

There is no shortage of research, Fischer added. Nearly 500 trials focused on PTSD are listed on clinicaltrials.gov are recruiting participants now or plan to soon.

Unsurprisingly, one of the primary drivers of PTSD therapeutics research is the VA. About 14% of the 5.7 million veterans who received care through the VA in 2023 had a diagnosis of PTSD.

“The US military is currently losing thousands of service members each year to PTSD- related disability discharges,” US Army Maj. Aaron Wolfgang, MD, a psychiatrist at the Walter Reed National Military Medical Center, said at the meeting. Only about 12%-20% of patients achieve remission with conventional therapies, added Wolfgang, who also is an assistant professor at the Uniformed Services University.

“For these reasons, establishing better treatments for PTSD is not only a matter of humanitarianism but also a pressing matter of national security,” he said.

The VA has committed at least $230 million to more than 140 active research projects in PTSD, Miriam J. Smyth, PhD, acting director of the clinical science, research and development service at the VA, said at the Reagan-Udall meeting.

One of the VA projects is the PTSD psychopharmacology initiative, which began in 2017 and now has 14 active clinical trials, said Smyth, who is also acting director for brain behavior and mental health at the VA. The first study should be finished by 2025.

The Million Veteran Program, with more than 1 million enrollees, has led to the discovery of genes related to re-experiencing traumatic memories and has confirmed that both PTSD and traumatic brain injury are risk factors for dementia, Smyth said.

The DoD has created a novel platform that establishes a common infrastructure for testing multiple drugs, called M-PACT. The platform allows sharing of placebo data across treatment arms. Drugs cycle off the platform if evidence indicates probability of success or failure.

Four trials are actively recruiting veterans and current service members. One is looking at vilazodone, approved in 2011 for major depressive disorder. It is being compared with placebo and fluoxetine in a trial that is currently recruiting.

Another trial will study daridorexant (sold as Quviviq), an orexin receptor antagonist, against placebo. The FDA approved daridorexant in 2022 as an insomnia treatment. A core issue in PTSD is sleep disruption, noted Davis.
 

New Therapies on the Way

Separately, Davis and colleagues are also studying methylphenidate, the stimulant used for attention-deficit/hyperactivity disorder. It may help with neurocognitive complaints and reduce PTSD symptoms, said Davis.

Because it is generic, few pharmaceutical manufacturers are likely to test it for PTSD, she said. But eventually, their work may lead a company to test newer stimulants for PTSD, she said.

Another potential therapeutic, BNC210, received Fast Track designation for PTSD from the FDA in 2019. Bionomics Limited in Australia will soon launch phase 3 trials of the investigational oral drug, which is a negative allosteric modulator of the alpha-7 nicotinic acetylcholine receptor. In late July, the company announced “ favorable feedback” from the agency on its phase 2 study, which led to the decision to move forward with larger trials.

Researchers at Brigham and Women’s Hospital have just reported that they may have found a target within the brain that will allow for transcranial magnetic stimulation (TMS) to ameliorate PTSD symptoms. They published results of a mapping effort in Nature Neuroscience and reported on one patient who had improved symptoms after receiving TMS for severe PTSD.

But perhaps one of the most promising treatments is a combination of sertraline and the new psychiatric medication brexpiprazole.

Brexpiprazole was developed by Otsuka Pharmaceutical and approved in the United States in 2015 as an adjunctive therapy to antidepressants for major depressive disorder and as a treatment for schizophrenia. In 2023, the FDA approved it for Alzheimer’s-related agitation. However, according to Otsuka, its mechanism of action is unknown.

Its efficacy may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, antagonist activity at serotonin 5-HT2A receptors, as well as antagonism of alpha-1B/2C receptors, said the company.

“It is the combination, rather than either alone, that’s going to have that broad synergistic pharmacology that is obviously potent for ameliorating the symptoms of PTSD,” said Davis, who has received consulting fees from Otsuka. “That’s an exciting development.”

Otsuka and partner Lundbeck Pharmaceuticals reported results in May from the companies’ phase 2 and 3 randomized clinical trials. The therapy achieved a statistically significant reduction (P <.05) in PTSD symptoms compared with sertraline plus placebo. This was without any supplemental psychotherapy.

The FDA accepted the companies’ new drug application in June and is expected to make a decision on approval in February 2025.
 

The Potential of Psychedelics

Though Lykos Therapeutics may have to go back to the drawing board on its MDMA-AT, psychedelics still have potential as PTSD therapies, Smyth said, who added that the VA is continuing to encourage study of MDMA and other psychedelic agents.

The VA issued a call for proposals for research on psychedelics in January, focused on MDMA or psilocybin in combination with psychotherapy. The administration received the first wave of applications early in the summer.

Scientific peer review panels made up of research experts from within and outside the VA have reviewed the applications and funding announcements are expected this fall, Smyth said.

Wolfgang, the Army psychiatrist, said, “Under the psychedelic treatment research clinical trial award, we welcome investigators to apply to what we anticipate will usher in a new era of innovation and hope for service members and their families who need it the most.”

Psychedelic studies are also proceeding without VA funding, as they have for years, when most of the trials were backed by universities or foundations or other private money. Johns Hopkins University is recruiting for a study in which patients would receive psilocybin along with trauma-focused psychotherapy, as is Ohio State University.

London-based Compass Pathways said in May that it successfully completed a phase 2 trial of Comp360, its synthetic psilocybin, in PTSD. The company has started a phase 3 study in treatment-resistant depression but has not given any further updates on PTSD.

Davis said that she believes that the FDA’s rejection of Lykos won’t lead to a shutdown of exploration of psychedelics.

“I think it informs these designs going forward, but it doesn’t eliminate that whole field of research,” she said.

Davis reported receiving consulting fees from Boehringer Ingelheim and Otsuka and research funding from Alkermes, the Patient-Centered Outcomes Research Institute, and the VA. Schnurr, Fischer, Smyth, and Wolfgang reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

It has been 24 years since a pharmaceutical was last approved for posttraumatic stress disorder (PTSD). The condition is notoriously difficult to treat, with up to 40% patients finding no relief from symptoms through psychotherapy or current medications.

Many clinicians, advocates, and patients had pinned their hopes on the psychedelic drug midomafetamine with assisted therapy (MDMA-AT). However, in August, the US Food and Drug Administration (FDA) rejected it. At this point, it’s unclear when the therapy will be available, if ever.

“Not getting the FDA approval of any drug at this point is a setback for the field,” Lori Davis, MD, a senior research psychiatrist at the Birmingham Veterans Affairs (VA) Health Care System in Birmingham, Alabama, told Medscape Medical News.

Having an FDA-approved product would have helped increase public awareness of PTSD and driven interest in developing new therapies, said Davis, who is also adjunct professor of psychiatry at the Heersink School of Medicine, University of Alabama at Birmingham.
 

A Treatable Condition

So with MDMA-AT off the table, where does the field go next? 

A public meeting in September hosted by the Reagan-Udall Foundation for the FDA in sought to answer that question. Agency officials joined representatives from the Department of Defense (DoD) and VA, patients, advocates, and industry representatives to discuss the current treatment landscape and what can be done to accelerate development of PTSD treatment.

Despite the common belief that PTSD is intractable, it “is a treatable condition,” Paula P. Schnurr, PhD, executive director of the VA National Center for PTSD, said at the meeting.

“There are effective treatments that work well for a lot of people, although not everyone has a satisfactory response,” she added.

The most effective psychotherapies are “trauma-focused,” and include cognitive processing therapy, eye movement desensitization and reprocessing, and prolonged exposure, according to the VA National Center for PTSD.

Three drugs have been approved by the FDA for PTSD: Venlafaxine (Effexor) in 1993, sertraline (Zoloft) in 1999, and paroxetine (Paxil) in 2000.

However, as the September meeting demonstrated, more therapies are needed.

“It’s clear to FDA and the federal government at large that there is an unmet need for safe and effective therapies to treat PTSD,” Bernard Fischer, MD, deputy director of the Division of Psychiatry in the Office of New Drugs at FDA’s Center for Drug Evaluation and Research, said at the meeting.

There is no shortage of research, Fischer added. Nearly 500 trials focused on PTSD are listed on clinicaltrials.gov are recruiting participants now or plan to soon.

Unsurprisingly, one of the primary drivers of PTSD therapeutics research is the VA. About 14% of the 5.7 million veterans who received care through the VA in 2023 had a diagnosis of PTSD.

“The US military is currently losing thousands of service members each year to PTSD- related disability discharges,” US Army Maj. Aaron Wolfgang, MD, a psychiatrist at the Walter Reed National Military Medical Center, said at the meeting. Only about 12%-20% of patients achieve remission with conventional therapies, added Wolfgang, who also is an assistant professor at the Uniformed Services University.

“For these reasons, establishing better treatments for PTSD is not only a matter of humanitarianism but also a pressing matter of national security,” he said.

The VA has committed at least $230 million to more than 140 active research projects in PTSD, Miriam J. Smyth, PhD, acting director of the clinical science, research and development service at the VA, said at the Reagan-Udall meeting.

One of the VA projects is the PTSD psychopharmacology initiative, which began in 2017 and now has 14 active clinical trials, said Smyth, who is also acting director for brain behavior and mental health at the VA. The first study should be finished by 2025.

The Million Veteran Program, with more than 1 million enrollees, has led to the discovery of genes related to re-experiencing traumatic memories and has confirmed that both PTSD and traumatic brain injury are risk factors for dementia, Smyth said.

The DoD has created a novel platform that establishes a common infrastructure for testing multiple drugs, called M-PACT. The platform allows sharing of placebo data across treatment arms. Drugs cycle off the platform if evidence indicates probability of success or failure.

Four trials are actively recruiting veterans and current service members. One is looking at vilazodone, approved in 2011 for major depressive disorder. It is being compared with placebo and fluoxetine in a trial that is currently recruiting.

Another trial will study daridorexant (sold as Quviviq), an orexin receptor antagonist, against placebo. The FDA approved daridorexant in 2022 as an insomnia treatment. A core issue in PTSD is sleep disruption, noted Davis.
 

New Therapies on the Way

Separately, Davis and colleagues are also studying methylphenidate, the stimulant used for attention-deficit/hyperactivity disorder. It may help with neurocognitive complaints and reduce PTSD symptoms, said Davis.

Because it is generic, few pharmaceutical manufacturers are likely to test it for PTSD, she said. But eventually, their work may lead a company to test newer stimulants for PTSD, she said.

Another potential therapeutic, BNC210, received Fast Track designation for PTSD from the FDA in 2019. Bionomics Limited in Australia will soon launch phase 3 trials of the investigational oral drug, which is a negative allosteric modulator of the alpha-7 nicotinic acetylcholine receptor. In late July, the company announced “ favorable feedback” from the agency on its phase 2 study, which led to the decision to move forward with larger trials.

Researchers at Brigham and Women’s Hospital have just reported that they may have found a target within the brain that will allow for transcranial magnetic stimulation (TMS) to ameliorate PTSD symptoms. They published results of a mapping effort in Nature Neuroscience and reported on one patient who had improved symptoms after receiving TMS for severe PTSD.

But perhaps one of the most promising treatments is a combination of sertraline and the new psychiatric medication brexpiprazole.

Brexpiprazole was developed by Otsuka Pharmaceutical and approved in the United States in 2015 as an adjunctive therapy to antidepressants for major depressive disorder and as a treatment for schizophrenia. In 2023, the FDA approved it for Alzheimer’s-related agitation. However, according to Otsuka, its mechanism of action is unknown.

Its efficacy may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, antagonist activity at serotonin 5-HT2A receptors, as well as antagonism of alpha-1B/2C receptors, said the company.

“It is the combination, rather than either alone, that’s going to have that broad synergistic pharmacology that is obviously potent for ameliorating the symptoms of PTSD,” said Davis, who has received consulting fees from Otsuka. “That’s an exciting development.”

Otsuka and partner Lundbeck Pharmaceuticals reported results in May from the companies’ phase 2 and 3 randomized clinical trials. The therapy achieved a statistically significant reduction (P <.05) in PTSD symptoms compared with sertraline plus placebo. This was without any supplemental psychotherapy.

The FDA accepted the companies’ new drug application in June and is expected to make a decision on approval in February 2025.
 

The Potential of Psychedelics

Though Lykos Therapeutics may have to go back to the drawing board on its MDMA-AT, psychedelics still have potential as PTSD therapies, Smyth said, who added that the VA is continuing to encourage study of MDMA and other psychedelic agents.

The VA issued a call for proposals for research on psychedelics in January, focused on MDMA or psilocybin in combination with psychotherapy. The administration received the first wave of applications early in the summer.

Scientific peer review panels made up of research experts from within and outside the VA have reviewed the applications and funding announcements are expected this fall, Smyth said.

Wolfgang, the Army psychiatrist, said, “Under the psychedelic treatment research clinical trial award, we welcome investigators to apply to what we anticipate will usher in a new era of innovation and hope for service members and their families who need it the most.”

Psychedelic studies are also proceeding without VA funding, as they have for years, when most of the trials were backed by universities or foundations or other private money. Johns Hopkins University is recruiting for a study in which patients would receive psilocybin along with trauma-focused psychotherapy, as is Ohio State University.

London-based Compass Pathways said in May that it successfully completed a phase 2 trial of Comp360, its synthetic psilocybin, in PTSD. The company has started a phase 3 study in treatment-resistant depression but has not given any further updates on PTSD.

Davis said that she believes that the FDA’s rejection of Lykos won’t lead to a shutdown of exploration of psychedelics.

“I think it informs these designs going forward, but it doesn’t eliminate that whole field of research,” she said.

Davis reported receiving consulting fees from Boehringer Ingelheim and Otsuka and research funding from Alkermes, the Patient-Centered Outcomes Research Institute, and the VA. Schnurr, Fischer, Smyth, and Wolfgang reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Clinicians receive conflicting advice on whether to order blood tests to screen for lipids in children. A new study could add to the confusion. Researchers found that a combination of physical proxy measures such as hypertension and body mass index (BMI) predicted the risk for future cardiovascular events as well as the physical model plus lipid labs, questioning the value of those blood tests.

Some medical organizations advise screening only for high-risk children because more research is needed to define the harms and benefits of universal screening. Diet and behavioral changes are sufficient for most children, and universal screening could lead to false positives and unnecessary further testing, they said.

Groups that favor lipid tests for all children say these measurements detect familial hypercholesterolemia (FH) that would not otherwise be diagnosed, leading to treatment with drugs like statins and a greater chance of preventing cardiovascular disease (CVD) in adulthood.

Researchers from the new study said their findings do not address screenings for FH, which affects 1 in 250 US children and puts them at a risk for atherosclerotic CVD.
 

Recommending Blood Tests in Age Groups

One of the seminal guidelines on screening lipids in children came from the National Heart, Lung, and Blood Institute (NHLBI), which in 2011 recommended children undergo dyslipidemia screening between the ages of 9 and 11 years and again between 17 and 21 years. Children should receive a screening starting at age 2 years if they have a family history of CVD or dyslipidemia or have diabetes, an elevated BMI, or hypertension. The American Academy of Pediatrics shortly followed suit, issuing similar recommendations.

Screening for the two subsets of ages was an expansion from the original 1992 guidelines from the National Cholesterol Education Program, which recommended screening only for children with either a family history of early CVD or elevated total cholesterol levels.

A 2011 panel for the NHLBI said the older approach identified significantly fewer children with abnormal levels of low-density lipoprotein cholesterol (LDL-C) than the addition of two age groups for screening, adding that many children do not have a complete family history. The American College of Cardiology and American Heart Association later supported NHLBI’s stance in their joint guidelines on the management of cholesterol.

Mark Corkins, MD, chair of the AAP’s Committee on Nutrition, told Medscape Medical News that if children are screened only because they have obesity or a family history of FH, some with elevated lipid levels will be missed. For instance, studies indicate caregiver recall of FH often is inaccurate, and the genetic disorder that causes the condition is not related to obesity.

“The screening is to find familial hypercholesterolemia, to try to find the ones that need therapy,” that would not be caught by the risk-based screening earlier on in childhood, Corkins said.
 

Only Screen Children With Risk Factors

But other groups do not agree. The US Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against screening for lipid disorders in asymptomatic children and teens.

The group also said it found inadequate evidence that lipid-lowering interventions in the general pediatric population lead to reductions in cardiovascular events or all-cause mortality once they reached adulthood. USPSTF also raised questions about the safety of lipid-lowering drugs in children.

“The current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger,” the panel wrote.

The American Academy of Family Physicians supports USPSTF’s recommendations.
 

Low Rate of Screening

While the uncertainty over screening in children continues, the practice has been adopted by a minority of clinicians.

A study published in JAMA Network Open in July found 9% of 700,000 9- to 11-year-olds had a documented result from a lipid screening. Among more than 1.3 million 17- to 21-year-olds, 13% had received a screening.

As BMI went up, so did screening rates. A little over 9% children and teens with a healthy weight were screened compared with 14.7% of those with moderate obesity and 21.9% of those with severe obesity.

Among those screened, 32.3% of 9- to 11-year-olds and 30.2% of 17- to 21-year-olds had abnormal lipid levels, defined as having one elevated measure out of five, including total cholesterol of 200 mg/dL or higher or LDL-C levels of 130 mg/dL or higher.

Justin Zachariah, MD, MPH, an associate professor of pediatrics-cardiology at Baylor College of Medicine in Houston, spoke about physicians screening children based only on factors like obesity during a presentation at the recent annual meeting of the American Academy of Pediatrics. He cited research showing roughly one in four children with abnormal lipids had a normal weight.

If a clinician is reserving a lipid screening for a child who is overweight or has obesity, “you’re missing nearly half the problem,” Zachariah said during his presentation.

One reason for the low rate of universal screening may be inattention to FH by clinicians, according to Samuel S. Gidding, MD, a professor in the Department of Genomic Health at Geisinger College of Health Sciences in Bridgewater Corners, Vermont.

For instance, a clinician has only a set amount of time during a well-child visit and other issues may take precedence, “so it doesn’t make sense to broach preventive screening for something that could happen 30 or 40 years from now, vs this [other] very immediate problem,” he said.

Clinicians “are triggered to act on the LDL level, but don’t think about FH as a possible diagnosis,” Gidding told Medscape Medical News.

Another barrier is that in some settings, caregivers must take children and teens to another facility on a different day to fulfill an order for a lipid test.

“It’s reluctance of doctors to order it, knowing patients won’t go through with it,” Gidding said.

Gidding is a consultant for Esperion Therapeutics. Other sources in this story reported no relevant financial conflicts of interest.
 

A version of this article first appeared on Medscape.com.

Clinicians receive conflicting advice on whether to order blood tests to screen for lipids in children. A new study could add to the confusion. Researchers found that a combination of physical proxy measures such as hypertension and body mass index (BMI) predicted the risk for future cardiovascular events as well as the physical model plus lipid labs, questioning the value of those blood tests.

Some medical organizations advise screening only for high-risk children because more research is needed to define the harms and benefits of universal screening. Diet and behavioral changes are sufficient for most children, and universal screening could lead to false positives and unnecessary further testing, they said.

Groups that favor lipid tests for all children say these measurements detect familial hypercholesterolemia (FH) that would not otherwise be diagnosed, leading to treatment with drugs like statins and a greater chance of preventing cardiovascular disease (CVD) in adulthood.

Researchers from the new study said their findings do not address screenings for FH, which affects 1 in 250 US children and puts them at a risk for atherosclerotic CVD.
 

Recommending Blood Tests in Age Groups

One of the seminal guidelines on screening lipids in children came from the National Heart, Lung, and Blood Institute (NHLBI), which in 2011 recommended children undergo dyslipidemia screening between the ages of 9 and 11 years and again between 17 and 21 years. Children should receive a screening starting at age 2 years if they have a family history of CVD or dyslipidemia or have diabetes, an elevated BMI, or hypertension. The American Academy of Pediatrics shortly followed suit, issuing similar recommendations.

Screening for the two subsets of ages was an expansion from the original 1992 guidelines from the National Cholesterol Education Program, which recommended screening only for children with either a family history of early CVD or elevated total cholesterol levels.

A 2011 panel for the NHLBI said the older approach identified significantly fewer children with abnormal levels of low-density lipoprotein cholesterol (LDL-C) than the addition of two age groups for screening, adding that many children do not have a complete family history. The American College of Cardiology and American Heart Association later supported NHLBI’s stance in their joint guidelines on the management of cholesterol.

Mark Corkins, MD, chair of the AAP’s Committee on Nutrition, told Medscape Medical News that if children are screened only because they have obesity or a family history of FH, some with elevated lipid levels will be missed. For instance, studies indicate caregiver recall of FH often is inaccurate, and the genetic disorder that causes the condition is not related to obesity.

“The screening is to find familial hypercholesterolemia, to try to find the ones that need therapy,” that would not be caught by the risk-based screening earlier on in childhood, Corkins said.
 

Only Screen Children With Risk Factors

But other groups do not agree. The US Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against screening for lipid disorders in asymptomatic children and teens.

The group also said it found inadequate evidence that lipid-lowering interventions in the general pediatric population lead to reductions in cardiovascular events or all-cause mortality once they reached adulthood. USPSTF also raised questions about the safety of lipid-lowering drugs in children.

“The current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger,” the panel wrote.

The American Academy of Family Physicians supports USPSTF’s recommendations.
 

Low Rate of Screening

While the uncertainty over screening in children continues, the practice has been adopted by a minority of clinicians.

A study published in JAMA Network Open in July found 9% of 700,000 9- to 11-year-olds had a documented result from a lipid screening. Among more than 1.3 million 17- to 21-year-olds, 13% had received a screening.

As BMI went up, so did screening rates. A little over 9% children and teens with a healthy weight were screened compared with 14.7% of those with moderate obesity and 21.9% of those with severe obesity.

Among those screened, 32.3% of 9- to 11-year-olds and 30.2% of 17- to 21-year-olds had abnormal lipid levels, defined as having one elevated measure out of five, including total cholesterol of 200 mg/dL or higher or LDL-C levels of 130 mg/dL or higher.

Justin Zachariah, MD, MPH, an associate professor of pediatrics-cardiology at Baylor College of Medicine in Houston, spoke about physicians screening children based only on factors like obesity during a presentation at the recent annual meeting of the American Academy of Pediatrics. He cited research showing roughly one in four children with abnormal lipids had a normal weight.

If a clinician is reserving a lipid screening for a child who is overweight or has obesity, “you’re missing nearly half the problem,” Zachariah said during his presentation.

One reason for the low rate of universal screening may be inattention to FH by clinicians, according to Samuel S. Gidding, MD, a professor in the Department of Genomic Health at Geisinger College of Health Sciences in Bridgewater Corners, Vermont.

For instance, a clinician has only a set amount of time during a well-child visit and other issues may take precedence, “so it doesn’t make sense to broach preventive screening for something that could happen 30 or 40 years from now, vs this [other] very immediate problem,” he said.

Clinicians “are triggered to act on the LDL level, but don’t think about FH as a possible diagnosis,” Gidding told Medscape Medical News.

Another barrier is that in some settings, caregivers must take children and teens to another facility on a different day to fulfill an order for a lipid test.

“It’s reluctance of doctors to order it, knowing patients won’t go through with it,” Gidding said.

Gidding is a consultant for Esperion Therapeutics. Other sources in this story reported no relevant financial conflicts of interest.
 

A version of this article first appeared on Medscape.com.

Clinicians receive conflicting advice on whether to order blood tests to screen for lipids in children. A new study could add to the confusion. Researchers found that a combination of physical proxy measures such as hypertension and body mass index (BMI) predicted the risk for future cardiovascular events as well as the physical model plus lipid labs, questioning the value of those blood tests.

Some medical organizations advise screening only for high-risk children because more research is needed to define the harms and benefits of universal screening. Diet and behavioral changes are sufficient for most children, and universal screening could lead to false positives and unnecessary further testing, they said.

Groups that favor lipid tests for all children say these measurements detect familial hypercholesterolemia (FH) that would not otherwise be diagnosed, leading to treatment with drugs like statins and a greater chance of preventing cardiovascular disease (CVD) in adulthood.

Researchers from the new study said their findings do not address screenings for FH, which affects 1 in 250 US children and puts them at a risk for atherosclerotic CVD.
 

Recommending Blood Tests in Age Groups

One of the seminal guidelines on screening lipids in children came from the National Heart, Lung, and Blood Institute (NHLBI), which in 2011 recommended children undergo dyslipidemia screening between the ages of 9 and 11 years and again between 17 and 21 years. Children should receive a screening starting at age 2 years if they have a family history of CVD or dyslipidemia or have diabetes, an elevated BMI, or hypertension. The American Academy of Pediatrics shortly followed suit, issuing similar recommendations.

Screening for the two subsets of ages was an expansion from the original 1992 guidelines from the National Cholesterol Education Program, which recommended screening only for children with either a family history of early CVD or elevated total cholesterol levels.

A 2011 panel for the NHLBI said the older approach identified significantly fewer children with abnormal levels of low-density lipoprotein cholesterol (LDL-C) than the addition of two age groups for screening, adding that many children do not have a complete family history. The American College of Cardiology and American Heart Association later supported NHLBI’s stance in their joint guidelines on the management of cholesterol.

Mark Corkins, MD, chair of the AAP’s Committee on Nutrition, told Medscape Medical News that if children are screened only because they have obesity or a family history of FH, some with elevated lipid levels will be missed. For instance, studies indicate caregiver recall of FH often is inaccurate, and the genetic disorder that causes the condition is not related to obesity.

“The screening is to find familial hypercholesterolemia, to try to find the ones that need therapy,” that would not be caught by the risk-based screening earlier on in childhood, Corkins said.
 

Only Screen Children With Risk Factors

But other groups do not agree. The US Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against screening for lipid disorders in asymptomatic children and teens.

The group also said it found inadequate evidence that lipid-lowering interventions in the general pediatric population lead to reductions in cardiovascular events or all-cause mortality once they reached adulthood. USPSTF also raised questions about the safety of lipid-lowering drugs in children.

“The current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger,” the panel wrote.

The American Academy of Family Physicians supports USPSTF’s recommendations.
 

Low Rate of Screening

While the uncertainty over screening in children continues, the practice has been adopted by a minority of clinicians.

A study published in JAMA Network Open in July found 9% of 700,000 9- to 11-year-olds had a documented result from a lipid screening. Among more than 1.3 million 17- to 21-year-olds, 13% had received a screening.

As BMI went up, so did screening rates. A little over 9% children and teens with a healthy weight were screened compared with 14.7% of those with moderate obesity and 21.9% of those with severe obesity.

Among those screened, 32.3% of 9- to 11-year-olds and 30.2% of 17- to 21-year-olds had abnormal lipid levels, defined as having one elevated measure out of five, including total cholesterol of 200 mg/dL or higher or LDL-C levels of 130 mg/dL or higher.

Justin Zachariah, MD, MPH, an associate professor of pediatrics-cardiology at Baylor College of Medicine in Houston, spoke about physicians screening children based only on factors like obesity during a presentation at the recent annual meeting of the American Academy of Pediatrics. He cited research showing roughly one in four children with abnormal lipids had a normal weight.

If a clinician is reserving a lipid screening for a child who is overweight or has obesity, “you’re missing nearly half the problem,” Zachariah said during his presentation.

One reason for the low rate of universal screening may be inattention to FH by clinicians, according to Samuel S. Gidding, MD, a professor in the Department of Genomic Health at Geisinger College of Health Sciences in Bridgewater Corners, Vermont.

For instance, a clinician has only a set amount of time during a well-child visit and other issues may take precedence, “so it doesn’t make sense to broach preventive screening for something that could happen 30 or 40 years from now, vs this [other] very immediate problem,” he said.

Clinicians “are triggered to act on the LDL level, but don’t think about FH as a possible diagnosis,” Gidding told Medscape Medical News.

Another barrier is that in some settings, caregivers must take children and teens to another facility on a different day to fulfill an order for a lipid test.

“It’s reluctance of doctors to order it, knowing patients won’t go through with it,” Gidding said.

Gidding is a consultant for Esperion Therapeutics. Other sources in this story reported no relevant financial conflicts of interest.
 

A version of this article first appeared on Medscape.com.

Katie Sullivan, DNP, FNP-C, is publicizing her own challenge with updating an insulin pump as part of an effort to bring an end to the biannual seasonal clock changes in the United States.

On March 10, 2024, Sullivan, who works in the Endocrinology Clinic, Michigan State University, East Lansing, Michigan, mistakenly reversed the AM and PM settings while adjusting her own insulin pump. Sullivan, who has type 1 diabetes, noticed several hours later that her blood glucose levels had become higher than usual and was surprised to see her pump showed sleep mode during the day.

She was able to address this glitch before going to sleep and thus “escaped a potential occurrence of nocturnal hypoglycemia,” Sullivan and her colleague, Saleh Aldasouqi, MD, wrote in a September commentary in the journal Clinical Diabetes.

The risk of daylight saving time (DST) changes for people with insulin pumps is well known. Aldasouqi himself raised it in a 2014 article in the Journal of Diabetes Science and Technology.

Medtronic Inc., the leading maker of insulin pumps, told this news organization in an email that it intends for future devices to automate DST changes. The company did not provide any further details on when such changes would happen.

For now, Medtronic and other makers of insulin pumps join in twice-a-year efforts to remind people they need to update their devices to adjust for DST changes. They will need to gear up these outreach campaigns, which include social media posts, again ahead of the end of DST on November 3, when clocks shift back an hour. Diabetes clinics and hospitals also send notes to patients.

Even so, people will fail to make this change or to do it correctly.

“Despite our efforts to educate our patients about DST glitches, we have detected incorrect time settings in some of our patients’ insulin pumps after the DST changes in the fall and spring and occasional cases of incorrect insulin dosing, resulting in hyperglycemia or hypoglycemia,” Sullivan and Aldasouqi wrote in their article.

The US Food and Drug Administration (FDA) database of injuries and mishaps with devices contains many reports about patients not adjusting their insulin pumps for DST.

Known as Manufacturer and User Facility Device Experience (MAUDE), this database does not provide identifying details about the patients. Instead, the reports contain only a few lines describing what happened. In many cases, people were able to easily resolve their temporary glycemic issues and then set their devices to the correct time.

But some of the MAUDE reports tell of more severe consequences, with people ending up in emergency rooms because they did not adjust their insulin pumps for DST.

Among these is a report about a November 2022 incident, where a patient suffered due to what appeared to be inaccurate continuous glucose monitor readings, combined with the effects of an insulin pump that had not been updated for a DST change.

Although that patient’s mother was available to assist and the patient consumed three dextrose candies, the patient still reportedly lost consciousness and experienced tremors. That led to hospitalization, where the patient was treated with intravenous saline, intravenous insulin, saline fluids, and insulin fluids. The patient left the hospital with “the issue resolved and no permanent damage” but then switched to another method of insulin therapy, the MAUDE report said.

It’s unclear how often DST changes lead to problems with insulin pumps, reflecting difficulties in tracking flaws and glitches in medical devices, Madris Kinard, the chief executive officer and founder of Device Events, told this news organization.

The FDA relies heavily on passive surveillance, gathering MAUDE reports submitted by companies, clinicians, and patients. That means many cases likely are missed, said Kinard who earlier worked as an analyst at the FDA, updating processes and systems to help identify risky devices.

For example, Sullivan told this news organization she had not filed a report for her incident with the insulin pump.
 

Permanent Standard Time?

Many clinicians, including Aldasouqi and Sullivan, argue a better solution to these challenges would be to end DST.

In their Clinical Diabetes article, they also cited other health risks associated with clock changes such as fatigue, headache, and loss of attention and alertness that can result in injuries.

But a permanent time change is a “politically charged issue, and it continues to be debated nationally and at the state level,” they wrote.

At least 30 states also considered measures this year related to DST, according to the National Conference of State Legislatures. A pending Senate bill intended to make DST permanent has the support of 8 Democrats and 11 Republicans, including Sen. Tommy Tuberville (R-Ala).

“It’s amazing how many phone calls we get over this one topic. People across America agree that changing our clocks back and forth twice a year really makes no sense,” Tuberville said last year on the Senate floor. “People call and say they’re just sick of it.”

These federal and state efforts have stalled to date on the key question of whether to make either standard time or DST permanent, the National Conference of State Legislatures noted. A shift to permanent DST might have benefits for some agricultural and recreational industries, but many physicians say it would be bad for people’s health.

The American Academy of Sleep Medicine (AASM) argues strongly for moving to permanent standard time. In a position statement published in the Journal of Clinical Sleep Medicine, the group said the acute transitions from standard time to DST pose harms, citing research indicating increased risks for adverse cardiovascular events, mood disorders, and motor vehicle crashes.

The solution is to end shifts in time and opt for standard time, which best aligns with the human biological clock, AASM said.

AASM noted that there already was a failed experiment in the United States with a shift to permanent DST. Congress established this in response to the 1973 OPEC oil embargo, expecting that allowing more evening hours with light would lead to energy savings. That didn’t pay off in the expected reduction in energy and the policy was highly unpopular, especially in rural areas, AASM said.

“After a single winter, the policy was reversed by an overwhelming congressional majority,” wrote Muhammad Adeel Rishi, MD, and other authors of the statement. “The unpopularity of the act was likely because despite greater evening light, the policy resulted in a greater proportion of days that required waking up on dark mornings, particularly in the winter.”

Karin G. Johnson, MD, professor of neurology at the UMass Chan School of Medicine, Worcester, Massachusetts, told this news organization that a shift to permanent DST would rob many people of the signals their bodies need for sleep.

“Sunrises and sunsets are later and that creates a desire for our body to stay up later and have more trouble getting up in the morning,” Johnson said. “You’re all but making it impossible for certain segments of the population to get enough sleep” with permanent DST.

Johnson, Sullivan, and Aldasouqi had no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Katie Sullivan, DNP, FNP-C, is publicizing her own challenge with updating an insulin pump as part of an effort to bring an end to the biannual seasonal clock changes in the United States.

On March 10, 2024, Sullivan, who works in the Endocrinology Clinic, Michigan State University, East Lansing, Michigan, mistakenly reversed the AM and PM settings while adjusting her own insulin pump. Sullivan, who has type 1 diabetes, noticed several hours later that her blood glucose levels had become higher than usual and was surprised to see her pump showed sleep mode during the day.

She was able to address this glitch before going to sleep and thus “escaped a potential occurrence of nocturnal hypoglycemia,” Sullivan and her colleague, Saleh Aldasouqi, MD, wrote in a September commentary in the journal Clinical Diabetes.

The risk of daylight saving time (DST) changes for people with insulin pumps is well known. Aldasouqi himself raised it in a 2014 article in the Journal of Diabetes Science and Technology.

Medtronic Inc., the leading maker of insulin pumps, told this news organization in an email that it intends for future devices to automate DST changes. The company did not provide any further details on when such changes would happen.

For now, Medtronic and other makers of insulin pumps join in twice-a-year efforts to remind people they need to update their devices to adjust for DST changes. They will need to gear up these outreach campaigns, which include social media posts, again ahead of the end of DST on November 3, when clocks shift back an hour. Diabetes clinics and hospitals also send notes to patients.

Even so, people will fail to make this change or to do it correctly.

“Despite our efforts to educate our patients about DST glitches, we have detected incorrect time settings in some of our patients’ insulin pumps after the DST changes in the fall and spring and occasional cases of incorrect insulin dosing, resulting in hyperglycemia or hypoglycemia,” Sullivan and Aldasouqi wrote in their article.

The US Food and Drug Administration (FDA) database of injuries and mishaps with devices contains many reports about patients not adjusting their insulin pumps for DST.

Known as Manufacturer and User Facility Device Experience (MAUDE), this database does not provide identifying details about the patients. Instead, the reports contain only a few lines describing what happened. In many cases, people were able to easily resolve their temporary glycemic issues and then set their devices to the correct time.

But some of the MAUDE reports tell of more severe consequences, with people ending up in emergency rooms because they did not adjust their insulin pumps for DST.

Among these is a report about a November 2022 incident, where a patient suffered due to what appeared to be inaccurate continuous glucose monitor readings, combined with the effects of an insulin pump that had not been updated for a DST change.

Although that patient’s mother was available to assist and the patient consumed three dextrose candies, the patient still reportedly lost consciousness and experienced tremors. That led to hospitalization, where the patient was treated with intravenous saline, intravenous insulin, saline fluids, and insulin fluids. The patient left the hospital with “the issue resolved and no permanent damage” but then switched to another method of insulin therapy, the MAUDE report said.

It’s unclear how often DST changes lead to problems with insulin pumps, reflecting difficulties in tracking flaws and glitches in medical devices, Madris Kinard, the chief executive officer and founder of Device Events, told this news organization.

The FDA relies heavily on passive surveillance, gathering MAUDE reports submitted by companies, clinicians, and patients. That means many cases likely are missed, said Kinard who earlier worked as an analyst at the FDA, updating processes and systems to help identify risky devices.

For example, Sullivan told this news organization she had not filed a report for her incident with the insulin pump.
 

Permanent Standard Time?

Many clinicians, including Aldasouqi and Sullivan, argue a better solution to these challenges would be to end DST.

In their Clinical Diabetes article, they also cited other health risks associated with clock changes such as fatigue, headache, and loss of attention and alertness that can result in injuries.

But a permanent time change is a “politically charged issue, and it continues to be debated nationally and at the state level,” they wrote.

At least 30 states also considered measures this year related to DST, according to the National Conference of State Legislatures. A pending Senate bill intended to make DST permanent has the support of 8 Democrats and 11 Republicans, including Sen. Tommy Tuberville (R-Ala).

“It’s amazing how many phone calls we get over this one topic. People across America agree that changing our clocks back and forth twice a year really makes no sense,” Tuberville said last year on the Senate floor. “People call and say they’re just sick of it.”

These federal and state efforts have stalled to date on the key question of whether to make either standard time or DST permanent, the National Conference of State Legislatures noted. A shift to permanent DST might have benefits for some agricultural and recreational industries, but many physicians say it would be bad for people’s health.

The American Academy of Sleep Medicine (AASM) argues strongly for moving to permanent standard time. In a position statement published in the Journal of Clinical Sleep Medicine, the group said the acute transitions from standard time to DST pose harms, citing research indicating increased risks for adverse cardiovascular events, mood disorders, and motor vehicle crashes.

The solution is to end shifts in time and opt for standard time, which best aligns with the human biological clock, AASM said.

AASM noted that there already was a failed experiment in the United States with a shift to permanent DST. Congress established this in response to the 1973 OPEC oil embargo, expecting that allowing more evening hours with light would lead to energy savings. That didn’t pay off in the expected reduction in energy and the policy was highly unpopular, especially in rural areas, AASM said.

“After a single winter, the policy was reversed by an overwhelming congressional majority,” wrote Muhammad Adeel Rishi, MD, and other authors of the statement. “The unpopularity of the act was likely because despite greater evening light, the policy resulted in a greater proportion of days that required waking up on dark mornings, particularly in the winter.”

Karin G. Johnson, MD, professor of neurology at the UMass Chan School of Medicine, Worcester, Massachusetts, told this news organization that a shift to permanent DST would rob many people of the signals their bodies need for sleep.

“Sunrises and sunsets are later and that creates a desire for our body to stay up later and have more trouble getting up in the morning,” Johnson said. “You’re all but making it impossible for certain segments of the population to get enough sleep” with permanent DST.

Johnson, Sullivan, and Aldasouqi had no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Katie Sullivan, DNP, FNP-C, is publicizing her own challenge with updating an insulin pump as part of an effort to bring an end to the biannual seasonal clock changes in the United States.

On March 10, 2024, Sullivan, who works in the Endocrinology Clinic, Michigan State University, East Lansing, Michigan, mistakenly reversed the AM and PM settings while adjusting her own insulin pump. Sullivan, who has type 1 diabetes, noticed several hours later that her blood glucose levels had become higher than usual and was surprised to see her pump showed sleep mode during the day.

She was able to address this glitch before going to sleep and thus “escaped a potential occurrence of nocturnal hypoglycemia,” Sullivan and her colleague, Saleh Aldasouqi, MD, wrote in a September commentary in the journal Clinical Diabetes.

The risk of daylight saving time (DST) changes for people with insulin pumps is well known. Aldasouqi himself raised it in a 2014 article in the Journal of Diabetes Science and Technology.

Medtronic Inc., the leading maker of insulin pumps, told this news organization in an email that it intends for future devices to automate DST changes. The company did not provide any further details on when such changes would happen.

For now, Medtronic and other makers of insulin pumps join in twice-a-year efforts to remind people they need to update their devices to adjust for DST changes. They will need to gear up these outreach campaigns, which include social media posts, again ahead of the end of DST on November 3, when clocks shift back an hour. Diabetes clinics and hospitals also send notes to patients.

Even so, people will fail to make this change or to do it correctly.

“Despite our efforts to educate our patients about DST glitches, we have detected incorrect time settings in some of our patients’ insulin pumps after the DST changes in the fall and spring and occasional cases of incorrect insulin dosing, resulting in hyperglycemia or hypoglycemia,” Sullivan and Aldasouqi wrote in their article.

The US Food and Drug Administration (FDA) database of injuries and mishaps with devices contains many reports about patients not adjusting their insulin pumps for DST.

Known as Manufacturer and User Facility Device Experience (MAUDE), this database does not provide identifying details about the patients. Instead, the reports contain only a few lines describing what happened. In many cases, people were able to easily resolve their temporary glycemic issues and then set their devices to the correct time.

But some of the MAUDE reports tell of more severe consequences, with people ending up in emergency rooms because they did not adjust their insulin pumps for DST.

Among these is a report about a November 2022 incident, where a patient suffered due to what appeared to be inaccurate continuous glucose monitor readings, combined with the effects of an insulin pump that had not been updated for a DST change.

Although that patient’s mother was available to assist and the patient consumed three dextrose candies, the patient still reportedly lost consciousness and experienced tremors. That led to hospitalization, where the patient was treated with intravenous saline, intravenous insulin, saline fluids, and insulin fluids. The patient left the hospital with “the issue resolved and no permanent damage” but then switched to another method of insulin therapy, the MAUDE report said.

It’s unclear how often DST changes lead to problems with insulin pumps, reflecting difficulties in tracking flaws and glitches in medical devices, Madris Kinard, the chief executive officer and founder of Device Events, told this news organization.

The FDA relies heavily on passive surveillance, gathering MAUDE reports submitted by companies, clinicians, and patients. That means many cases likely are missed, said Kinard who earlier worked as an analyst at the FDA, updating processes and systems to help identify risky devices.

For example, Sullivan told this news organization she had not filed a report for her incident with the insulin pump.
 

Permanent Standard Time?

Many clinicians, including Aldasouqi and Sullivan, argue a better solution to these challenges would be to end DST.

In their Clinical Diabetes article, they also cited other health risks associated with clock changes such as fatigue, headache, and loss of attention and alertness that can result in injuries.

But a permanent time change is a “politically charged issue, and it continues to be debated nationally and at the state level,” they wrote.

At least 30 states also considered measures this year related to DST, according to the National Conference of State Legislatures. A pending Senate bill intended to make DST permanent has the support of 8 Democrats and 11 Republicans, including Sen. Tommy Tuberville (R-Ala).

“It’s amazing how many phone calls we get over this one topic. People across America agree that changing our clocks back and forth twice a year really makes no sense,” Tuberville said last year on the Senate floor. “People call and say they’re just sick of it.”

These federal and state efforts have stalled to date on the key question of whether to make either standard time or DST permanent, the National Conference of State Legislatures noted. A shift to permanent DST might have benefits for some agricultural and recreational industries, but many physicians say it would be bad for people’s health.

The American Academy of Sleep Medicine (AASM) argues strongly for moving to permanent standard time. In a position statement published in the Journal of Clinical Sleep Medicine, the group said the acute transitions from standard time to DST pose harms, citing research indicating increased risks for adverse cardiovascular events, mood disorders, and motor vehicle crashes.

The solution is to end shifts in time and opt for standard time, which best aligns with the human biological clock, AASM said.

AASM noted that there already was a failed experiment in the United States with a shift to permanent DST. Congress established this in response to the 1973 OPEC oil embargo, expecting that allowing more evening hours with light would lead to energy savings. That didn’t pay off in the expected reduction in energy and the policy was highly unpopular, especially in rural areas, AASM said.

“After a single winter, the policy was reversed by an overwhelming congressional majority,” wrote Muhammad Adeel Rishi, MD, and other authors of the statement. “The unpopularity of the act was likely because despite greater evening light, the policy resulted in a greater proportion of days that required waking up on dark mornings, particularly in the winter.”

Karin G. Johnson, MD, professor of neurology at the UMass Chan School of Medicine, Worcester, Massachusetts, told this news organization that a shift to permanent DST would rob many people of the signals their bodies need for sleep.

“Sunrises and sunsets are later and that creates a desire for our body to stay up later and have more trouble getting up in the morning,” Johnson said. “You’re all but making it impossible for certain segments of the population to get enough sleep” with permanent DST.

Johnson, Sullivan, and Aldasouqi had no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Researchers may be on track to develop a much-needed tool for studying endometriosis: A noninvasive stool test that could replace the current gold standard of laparoscopy.

Their approach, which focuses on the link between the gut microbiome and endometriosis, also identified a bacterial metabolite they said might be developed as an oral medication for the condition, which affects at least 11% of women.

In previous research, Rama Kommagani, PhD, an associate professor in the Department of Pathology & Immunology at Baylor College of Medicine in Houston, Texas, worked with a mouse model in which endometrial tissue from donor rodents was injected into the peritoneal space of healthy rodents to induce the disorder.

Transfer of fecal microbiota from mice with endometriosis to those without the condition induced the trademark lesions, suggesting the microbiome influences the development of endometriosis. Treating the animals with the antibiotic metronidazole inhibited the progression of endometrial lesions.

Kommagani speculated the microbes release metabolites that stimulate the growth of the endometrial lesions. “Bad bacteria release metabolites, you know, which actually promote the disease,” Kommagani said. “But the good bacteria might release some protective metabolites such as short-chain fatty acids.”

In a new study, Kommagani and his colleagues sought to identify a unique profile of bacteria-derived metabolites that could reliably diagnose endometriosis. Using stool specimens from 18 women with the condition and 31 without the disease, his team conducted whole metabolic profiling of the gut microbiota.

After identifying hundreds of metabolites in the samples, further analysis revealed a subset of 12 metabolites that consistently differentiated women with and without endometriosis.

These findings led to more questions. “If a metabolite is lower in women with endometriosis, does it have any functional relevance?” Kommagani said.

One candidate was 4-hydroxyindole (4HI), which was found in lower levels in the stool of patients. This substance is a little-understood derivative of its parent compound, indole, which occurs naturally in plants and has a wide range of therapeutic uses.

Using a mouse model, Kommagani’s lab demonstrated that feeding mice 4HI before receiving an endometrial transplant prevented the development of lesions typical of endometriosis. Mice given 4HI after they had developed endometriosis showed regression of lesions and decreased response to painful stimuli.

“In a nutshell, we found a specific set of bacterial metabolites in stool, which could be used towards a noninvasive diagnostic test,” Kommagani said. “But we also found this distinct, specific metabolite that could be used as a therapeutic molecule.” 

Tatnai Burnett, MD, an assistant professor of obstetrics and gynecology at Mayo Clinic in Rochester, Minnesota, who is not associated with the study, said a noninvasive test would have several advantages over the current methods of diagnosing endometriosis. Clinicians could detect and treat women earlier in the course of their disease. Secondly, a test with sufficient negative predictive value would be helpful in deciding whether to initiate treatment with hormones or other oral medications or go straight to surgery. “I would choose not to do a surgery if I knew with enough certainty that I wasn’t going to find anything,” said Burnett.

Lastly, a test that was quantitative and showed a response to treatment could be used as a disease activity marker to monitor the course of someone’s treatment.

But Burnett said more data on the approach are necessary. “This is a fairly small study, as it goes, for developing a screening test,” he said. “We need to see what its positive predictive value, negative predictive value, sensitivity, and specificity are in a bigger group.”

The road to a cure is even longer than the path to developing a screening test. Kommagani’s lab is now conducting more studies in mice to elucidate the pharmacokinetics and toxicology of 4HI before human trials can be attempted.

And as Burnett pointed out, although mouse models are great for experimentation and generating hypotheses, “We’ve seen way too many times in the past where something’s really exciting in a mouse model or a rat model or a monkey model, and it just doesn’t pan out in humans.”

Kommagani received funding from National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society. Burnett reported no financial conflicts of interest.

A version of this article first appeared on Medscape.com.

Researchers may be on track to develop a much-needed tool for studying endometriosis: A noninvasive stool test that could replace the current gold standard of laparoscopy.

Their approach, which focuses on the link between the gut microbiome and endometriosis, also identified a bacterial metabolite they said might be developed as an oral medication for the condition, which affects at least 11% of women.

In previous research, Rama Kommagani, PhD, an associate professor in the Department of Pathology & Immunology at Baylor College of Medicine in Houston, Texas, worked with a mouse model in which endometrial tissue from donor rodents was injected into the peritoneal space of healthy rodents to induce the disorder.

Transfer of fecal microbiota from mice with endometriosis to those without the condition induced the trademark lesions, suggesting the microbiome influences the development of endometriosis. Treating the animals with the antibiotic metronidazole inhibited the progression of endometrial lesions.

Kommagani speculated the microbes release metabolites that stimulate the growth of the endometrial lesions. “Bad bacteria release metabolites, you know, which actually promote the disease,” Kommagani said. “But the good bacteria might release some protective metabolites such as short-chain fatty acids.”

In a new study, Kommagani and his colleagues sought to identify a unique profile of bacteria-derived metabolites that could reliably diagnose endometriosis. Using stool specimens from 18 women with the condition and 31 without the disease, his team conducted whole metabolic profiling of the gut microbiota.

After identifying hundreds of metabolites in the samples, further analysis revealed a subset of 12 metabolites that consistently differentiated women with and without endometriosis.

These findings led to more questions. “If a metabolite is lower in women with endometriosis, does it have any functional relevance?” Kommagani said.

One candidate was 4-hydroxyindole (4HI), which was found in lower levels in the stool of patients. This substance is a little-understood derivative of its parent compound, indole, which occurs naturally in plants and has a wide range of therapeutic uses.

Using a mouse model, Kommagani’s lab demonstrated that feeding mice 4HI before receiving an endometrial transplant prevented the development of lesions typical of endometriosis. Mice given 4HI after they had developed endometriosis showed regression of lesions and decreased response to painful stimuli.

“In a nutshell, we found a specific set of bacterial metabolites in stool, which could be used towards a noninvasive diagnostic test,” Kommagani said. “But we also found this distinct, specific metabolite that could be used as a therapeutic molecule.” 

Tatnai Burnett, MD, an assistant professor of obstetrics and gynecology at Mayo Clinic in Rochester, Minnesota, who is not associated with the study, said a noninvasive test would have several advantages over the current methods of diagnosing endometriosis. Clinicians could detect and treat women earlier in the course of their disease. Secondly, a test with sufficient negative predictive value would be helpful in deciding whether to initiate treatment with hormones or other oral medications or go straight to surgery. “I would choose not to do a surgery if I knew with enough certainty that I wasn’t going to find anything,” said Burnett.

Lastly, a test that was quantitative and showed a response to treatment could be used as a disease activity marker to monitor the course of someone’s treatment.

But Burnett said more data on the approach are necessary. “This is a fairly small study, as it goes, for developing a screening test,” he said. “We need to see what its positive predictive value, negative predictive value, sensitivity, and specificity are in a bigger group.”

The road to a cure is even longer than the path to developing a screening test. Kommagani’s lab is now conducting more studies in mice to elucidate the pharmacokinetics and toxicology of 4HI before human trials can be attempted.

And as Burnett pointed out, although mouse models are great for experimentation and generating hypotheses, “We’ve seen way too many times in the past where something’s really exciting in a mouse model or a rat model or a monkey model, and it just doesn’t pan out in humans.”

Kommagani received funding from National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society. Burnett reported no financial conflicts of interest.

A version of this article first appeared on Medscape.com.

Researchers may be on track to develop a much-needed tool for studying endometriosis: A noninvasive stool test that could replace the current gold standard of laparoscopy.

Their approach, which focuses on the link between the gut microbiome and endometriosis, also identified a bacterial metabolite they said might be developed as an oral medication for the condition, which affects at least 11% of women.

In previous research, Rama Kommagani, PhD, an associate professor in the Department of Pathology & Immunology at Baylor College of Medicine in Houston, Texas, worked with a mouse model in which endometrial tissue from donor rodents was injected into the peritoneal space of healthy rodents to induce the disorder.

Transfer of fecal microbiota from mice with endometriosis to those without the condition induced the trademark lesions, suggesting the microbiome influences the development of endometriosis. Treating the animals with the antibiotic metronidazole inhibited the progression of endometrial lesions.

Kommagani speculated the microbes release metabolites that stimulate the growth of the endometrial lesions. “Bad bacteria release metabolites, you know, which actually promote the disease,” Kommagani said. “But the good bacteria might release some protective metabolites such as short-chain fatty acids.”

In a new study, Kommagani and his colleagues sought to identify a unique profile of bacteria-derived metabolites that could reliably diagnose endometriosis. Using stool specimens from 18 women with the condition and 31 without the disease, his team conducted whole metabolic profiling of the gut microbiota.

After identifying hundreds of metabolites in the samples, further analysis revealed a subset of 12 metabolites that consistently differentiated women with and without endometriosis.

These findings led to more questions. “If a metabolite is lower in women with endometriosis, does it have any functional relevance?” Kommagani said.

One candidate was 4-hydroxyindole (4HI), which was found in lower levels in the stool of patients. This substance is a little-understood derivative of its parent compound, indole, which occurs naturally in plants and has a wide range of therapeutic uses.

Using a mouse model, Kommagani’s lab demonstrated that feeding mice 4HI before receiving an endometrial transplant prevented the development of lesions typical of endometriosis. Mice given 4HI after they had developed endometriosis showed regression of lesions and decreased response to painful stimuli.

“In a nutshell, we found a specific set of bacterial metabolites in stool, which could be used towards a noninvasive diagnostic test,” Kommagani said. “But we also found this distinct, specific metabolite that could be used as a therapeutic molecule.” 

Tatnai Burnett, MD, an assistant professor of obstetrics and gynecology at Mayo Clinic in Rochester, Minnesota, who is not associated with the study, said a noninvasive test would have several advantages over the current methods of diagnosing endometriosis. Clinicians could detect and treat women earlier in the course of their disease. Secondly, a test with sufficient negative predictive value would be helpful in deciding whether to initiate treatment with hormones or other oral medications or go straight to surgery. “I would choose not to do a surgery if I knew with enough certainty that I wasn’t going to find anything,” said Burnett.

Lastly, a test that was quantitative and showed a response to treatment could be used as a disease activity marker to monitor the course of someone’s treatment.

But Burnett said more data on the approach are necessary. “This is a fairly small study, as it goes, for developing a screening test,” he said. “We need to see what its positive predictive value, negative predictive value, sensitivity, and specificity are in a bigger group.”

The road to a cure is even longer than the path to developing a screening test. Kommagani’s lab is now conducting more studies in mice to elucidate the pharmacokinetics and toxicology of 4HI before human trials can be attempted.

And as Burnett pointed out, although mouse models are great for experimentation and generating hypotheses, “We’ve seen way too many times in the past where something’s really exciting in a mouse model or a rat model or a monkey model, and it just doesn’t pan out in humans.”

Kommagani received funding from National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society. Burnett reported no financial conflicts of interest.

A version of this article first appeared on Medscape.com.

Primary care physicians (PCPs) play a key role in treating young patients as they progress through the “atopic march” from atopic dermatitis through food allergy, asthma, and allergic rhinitis. They can also help prevent the process from starting.

“The PCP is usually the first clinician a family with concerns about atopic conditions sees, unless they first visit urgent care or an emergency department after an allergic reaction to food. Either way, families rely on their PCP for ongoing guidance,” said Terri F. Brown-Whitehorn, MD, attending physician in the Division of Allergy and Immunology at the Center for Pediatric Eosinophilic Disorders and the Integrative Health Program at Children’s Hospital of Philadelphia.

“The most important thing PCPs can do is know that the atopic march exists, how it progresses over time, and what signs and symptoms to look for,” she told this news organization.
 

The Atopic March

The atopic march describes the progression of allergic diseases in a child over time, with atopic dermatitis and food allergy in infancy tending to be followed by allergic rhinitis and asthma into later childhood and adulthood.

Although the pathophysiology of the inflammation that precedes atopic dermatitis is unclear, two main hypotheses have been proposed. The first suggests a primary immune dysfunction leads to immunoglobulin E (IgE) sensitization, allergic inflammation, and a secondary disturbance of the epithelial barrier; the second starts with a primary defect in the epithelial barrier that leads to secondary immunologic dysregulation and results in inflammation.

Genetics, infection, hygiene, extreme climate, food allergens, probiotics, aeroallergens, and tobacco smoke are thought to play roles in atopic dermatitis. An estimated 10%-12% of children and 1% of adults in the United States have been reported to have the condition, and the prevalence appears to be increasing. An estimated 85% of cases occur during the first year of life and 95% before the age of 5 years.

“Atopy often, though not always, runs in families, so PCPs should inquire about the history of atopic dermatitis, IgE-mediated food allergies, allergic rhinitis, and asthma in the patient’s siblings, parents, and grandparents,” Brown-Whitehorn said.
 

Key Educators

PCPs treat the full gamut of atopic conditions and are key educators on ways families can help mitigate their children’s atopic march or stop it before it begins, said Gerald Bell Lee, MD, an allergist and immunologist at Children’s Healthcare of Atlanta and an associate professor in the Division of Allergy and Immunology at Emory University School of Medicine, Atlanta.

“Most parents who bring their infants with eczema to the PCP assume their child ate something that caused their rash. But the relationship between atopic dermatitis, a type of eczema, and food allergy is more complicated,” he added.

Lee said PCPs should explain to their patients what atopic dermatitis is, how it starts and progresses, and how families can help prevent the condition by, for example, introducing allergenic foods to infants at around 4-6 months of age.
 

Atopic Dermatitis

PCPs should inform parents and other caregivers to wash their hands before moisturizing their child, take care not to contaminate the moisturizer, and bathe their child only when the child is dirty.

“Soap removes protective natural skin oils and increases moisture loss, and exposure to soap and bathing is a main contributor to eczema,” said Lee. “Dry skin loses its protective barrier, allowing outside agents to penetrate and be identified by the immune system.”

“According to one hypothesis, parents may eat food, not wash their hands afterwards, then moisturize their baby. This unhygienic practice spreads food proteins from the adult’s meal, and possibly from contaminants present in the moisturizer, all over the baby’s body,” he added.

Lee said he and his colleagues discourage overbathing babies to minimize the risk for skin injury that begins the atopic march: “New parents are inundated with infant skincare messaging and products. But we need to weigh societal pressures against practicality and ask, ‘Is the child’s skin actually dirty?’ ”

Atopic dermatitis tends to appear on the extensor surfaces, face, and scalp in infants and around arm and leg creases in toddlers and older children. Severe forms of the condition can be more widely distributed on the body, said Aarti P. Pandya, MD, medical director of the Food Allergy Center at Children’s Mercy Kansas City and clinical assistant professor of pediatrics at the University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.
 

Avoid Triggers, Minimize Flares

Triggers of eczema are varied and common. To help minimize flares, PCPs can encourage caregivers to avoid products with fragrances or dyes, minimize the use of soaps, and completely rinse laundry detergent from clothing and household items. “Advise them to keep fingernails short and control dander, pollen, mold, household chemicals, and tobacco smoke, as well as the child’s stress and anxiety, which can also be a trigger,” Lee said.

“Skin infections from organisms such as staph, herpes, or coxsackie can also exacerbate symptoms,” Brown-Whitehorn added. “PCPs can educate caregivers to avoid all known triggers and give them an ‘action plan’ to carry out when skin flares.”
 

Food Allergies

Parents may be unaware food allergens can travel far beyond the plate, Lee said. Researchers vacuuming household bedding, carpets, furniture, and other surfaces have detected unnoticeably tiny quantities of allergenic food proteins in ordinary house dust. Touching this dust appears to provide the main exposure to those allergens.

“According to the dual exposure to allergen hypothesis, an infant’s tolerance to antigens occurs through high-dose exposure by mouth, and allergic sensitization occurs through low-dose exposure through the skin,” he said. “As young as four to six months of age, even before eating solid food, a child develops eczema, has a leaky skin barrier, comes in contact with food, and develops a food allergy.”

IgE-mediated food allergies can begin at any age. “Symptoms occur when a food is ingested and the patient develops symptoms including but not limited to urticaria, angioedema, pruritus, flushing, vomiting, diarrhea, coughing, wheezing, difficulty breathing, presyncope, or syncope,” Pandya noted.

In the case of eosinophilic esophagitis, which may also be part of the atopic march, infants and toddlers often have challenging-to-treat symptoms of reflux, while school-age children have reflux and abdominal pain, and adolescents and adults may experience difficulty swallowing and impactions of food or pills, Brown-Whitehorn said.

To differentiate between food allergy and contact dermatitis, Lee suggested providers ask, “ ’Is the rash hives? If yes, is the rash generalized or in a limited area?’ Then consider the statistical probabilities. Skin problems after milk, egg, wheat, soy, peanut, tree nut, fish, shellfish, or sesame are likely due to IgE-mediated food allergy, but after ketchup or strawberry are probably from skin contact.”
 

Allergic Rhinitis and Asthma

“For asthma, ask about frequency of night cough and symptoms with exercise, laughing, or crying. For allergic rhinitis, look for runny nose, itchy eyes, or sneezing,” Brown-Whitehorn said.

Testing and Monitoring

Assessing the extent of eczema with the Eczema Area and Severity Index or the SCORing Atopic Dermatitis index takes time but may be necessary to obtain insurance coverage for treatments such as biologics.

Avoid ordering IgE food panels, which can result in false positives that can lead to loss of tolerance and nutritional deficiencies; psychological harm from bullying, anxiety, and decreased quality of life; and higher food and healthcare costs, Pandya said.

Treatments
Caregivers may be wary about treatments, and all the three experts this news organization spoke with stressed the importance of educating caregivers about how treatments work and what to expect from them.

“Early and aggressive atopic dermatitis treatment could prevent sensitization to food or aeroallergens, which could help prevent additional atopic diseases, including those on the atopic march,” Pandya said. “Topical steroids are considered first line at any age. Topical phosphodiesterase inhibitors are approved at 3 months of age and above. Topical calcineurin inhibitors are approved at 2 years of age and above. Wet wrap therapy and bleach baths can be effective. Other options include biologic therapy, allergen immunotherapy, and UV therapy.”

“Epinephrine auto-injectors can counteract food reactions. For allergic rhinitis, non-sedating antihistamines, steroidal nasal sprays, and nasal antihistamines help. Asthma treatments include various inhaled medications,” Brown-Whitehorn added.
 

When to Refer to Specialists

Involving an allergist, dermatologist, pulmonologist, or ear nose throat specialist to the patient’s care team is advisable in more challenging cases.

If a child is younger than 3 months and has moderate to severe atopic dermatitis, an underlying immune defect may be to blame, so an allergy and immunology assessment is warranted, Brown-Whitehorn said. “An allergist can help any child who has recurrent coughing or wheezing avoid the emergency room or hospitalization.”

“In pediatrics, we always try to find the medication, regimen, and avoidance strategies that use the least treatment to provide the best care for each patient,” Brown-Whitehorn added. “Children eat, play, learn, and sleep, and every stage of the atopic march affects each of these activities. As clinicians, we need to be sure that we are helping children make the best of all these activities.”

Brown-Whitehorn reported financial relationships with DBV Technologies and Regeneron Pharmaceuticals. Lee reported financial relationships with Novartis. Pandya reported financial relationships with DBV Technologies, Thermo Fisher Scientific, and Sanofi.
 

A version of this article first appeared on Medscape.com.

Primary care physicians (PCPs) play a key role in treating young patients as they progress through the “atopic march” from atopic dermatitis through food allergy, asthma, and allergic rhinitis. They can also help prevent the process from starting.

“The PCP is usually the first clinician a family with concerns about atopic conditions sees, unless they first visit urgent care or an emergency department after an allergic reaction to food. Either way, families rely on their PCP for ongoing guidance,” said Terri F. Brown-Whitehorn, MD, attending physician in the Division of Allergy and Immunology at the Center for Pediatric Eosinophilic Disorders and the Integrative Health Program at Children’s Hospital of Philadelphia.

“The most important thing PCPs can do is know that the atopic march exists, how it progresses over time, and what signs and symptoms to look for,” she told this news organization.
 

The Atopic March

The atopic march describes the progression of allergic diseases in a child over time, with atopic dermatitis and food allergy in infancy tending to be followed by allergic rhinitis and asthma into later childhood and adulthood.

Although the pathophysiology of the inflammation that precedes atopic dermatitis is unclear, two main hypotheses have been proposed. The first suggests a primary immune dysfunction leads to immunoglobulin E (IgE) sensitization, allergic inflammation, and a secondary disturbance of the epithelial barrier; the second starts with a primary defect in the epithelial barrier that leads to secondary immunologic dysregulation and results in inflammation.

Genetics, infection, hygiene, extreme climate, food allergens, probiotics, aeroallergens, and tobacco smoke are thought to play roles in atopic dermatitis. An estimated 10%-12% of children and 1% of adults in the United States have been reported to have the condition, and the prevalence appears to be increasing. An estimated 85% of cases occur during the first year of life and 95% before the age of 5 years.

“Atopy often, though not always, runs in families, so PCPs should inquire about the history of atopic dermatitis, IgE-mediated food allergies, allergic rhinitis, and asthma in the patient’s siblings, parents, and grandparents,” Brown-Whitehorn said.
 

Key Educators

PCPs treat the full gamut of atopic conditions and are key educators on ways families can help mitigate their children’s atopic march or stop it before it begins, said Gerald Bell Lee, MD, an allergist and immunologist at Children’s Healthcare of Atlanta and an associate professor in the Division of Allergy and Immunology at Emory University School of Medicine, Atlanta.

“Most parents who bring their infants with eczema to the PCP assume their child ate something that caused their rash. But the relationship between atopic dermatitis, a type of eczema, and food allergy is more complicated,” he added.

Lee said PCPs should explain to their patients what atopic dermatitis is, how it starts and progresses, and how families can help prevent the condition by, for example, introducing allergenic foods to infants at around 4-6 months of age.
 

Atopic Dermatitis

PCPs should inform parents and other caregivers to wash their hands before moisturizing their child, take care not to contaminate the moisturizer, and bathe their child only when the child is dirty.

“Soap removes protective natural skin oils and increases moisture loss, and exposure to soap and bathing is a main contributor to eczema,” said Lee. “Dry skin loses its protective barrier, allowing outside agents to penetrate and be identified by the immune system.”

“According to one hypothesis, parents may eat food, not wash their hands afterwards, then moisturize their baby. This unhygienic practice spreads food proteins from the adult’s meal, and possibly from contaminants present in the moisturizer, all over the baby’s body,” he added.

Lee said he and his colleagues discourage overbathing babies to minimize the risk for skin injury that begins the atopic march: “New parents are inundated with infant skincare messaging and products. But we need to weigh societal pressures against practicality and ask, ‘Is the child’s skin actually dirty?’ ”

Atopic dermatitis tends to appear on the extensor surfaces, face, and scalp in infants and around arm and leg creases in toddlers and older children. Severe forms of the condition can be more widely distributed on the body, said Aarti P. Pandya, MD, medical director of the Food Allergy Center at Children’s Mercy Kansas City and clinical assistant professor of pediatrics at the University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.
 

Avoid Triggers, Minimize Flares

Triggers of eczema are varied and common. To help minimize flares, PCPs can encourage caregivers to avoid products with fragrances or dyes, minimize the use of soaps, and completely rinse laundry detergent from clothing and household items. “Advise them to keep fingernails short and control dander, pollen, mold, household chemicals, and tobacco smoke, as well as the child’s stress and anxiety, which can also be a trigger,” Lee said.

“Skin infections from organisms such as staph, herpes, or coxsackie can also exacerbate symptoms,” Brown-Whitehorn added. “PCPs can educate caregivers to avoid all known triggers and give them an ‘action plan’ to carry out when skin flares.”
 

Food Allergies

Parents may be unaware food allergens can travel far beyond the plate, Lee said. Researchers vacuuming household bedding, carpets, furniture, and other surfaces have detected unnoticeably tiny quantities of allergenic food proteins in ordinary house dust. Touching this dust appears to provide the main exposure to those allergens.

“According to the dual exposure to allergen hypothesis, an infant’s tolerance to antigens occurs through high-dose exposure by mouth, and allergic sensitization occurs through low-dose exposure through the skin,” he said. “As young as four to six months of age, even before eating solid food, a child develops eczema, has a leaky skin barrier, comes in contact with food, and develops a food allergy.”

IgE-mediated food allergies can begin at any age. “Symptoms occur when a food is ingested and the patient develops symptoms including but not limited to urticaria, angioedema, pruritus, flushing, vomiting, diarrhea, coughing, wheezing, difficulty breathing, presyncope, or syncope,” Pandya noted.

In the case of eosinophilic esophagitis, which may also be part of the atopic march, infants and toddlers often have challenging-to-treat symptoms of reflux, while school-age children have reflux and abdominal pain, and adolescents and adults may experience difficulty swallowing and impactions of food or pills, Brown-Whitehorn said.

To differentiate between food allergy and contact dermatitis, Lee suggested providers ask, “ ’Is the rash hives? If yes, is the rash generalized or in a limited area?’ Then consider the statistical probabilities. Skin problems after milk, egg, wheat, soy, peanut, tree nut, fish, shellfish, or sesame are likely due to IgE-mediated food allergy, but after ketchup or strawberry are probably from skin contact.”
 

Allergic Rhinitis and Asthma

“For asthma, ask about frequency of night cough and symptoms with exercise, laughing, or crying. For allergic rhinitis, look for runny nose, itchy eyes, or sneezing,” Brown-Whitehorn said.

Testing and Monitoring

Assessing the extent of eczema with the Eczema Area and Severity Index or the SCORing Atopic Dermatitis index takes time but may be necessary to obtain insurance coverage for treatments such as biologics.

Avoid ordering IgE food panels, which can result in false positives that can lead to loss of tolerance and nutritional deficiencies; psychological harm from bullying, anxiety, and decreased quality of life; and higher food and healthcare costs, Pandya said.

Treatments
Caregivers may be wary about treatments, and all the three experts this news organization spoke with stressed the importance of educating caregivers about how treatments work and what to expect from them.

“Early and aggressive atopic dermatitis treatment could prevent sensitization to food or aeroallergens, which could help prevent additional atopic diseases, including those on the atopic march,” Pandya said. “Topical steroids are considered first line at any age. Topical phosphodiesterase inhibitors are approved at 3 months of age and above. Topical calcineurin inhibitors are approved at 2 years of age and above. Wet wrap therapy and bleach baths can be effective. Other options include biologic therapy, allergen immunotherapy, and UV therapy.”

“Epinephrine auto-injectors can counteract food reactions. For allergic rhinitis, non-sedating antihistamines, steroidal nasal sprays, and nasal antihistamines help. Asthma treatments include various inhaled medications,” Brown-Whitehorn added.
 

When to Refer to Specialists

Involving an allergist, dermatologist, pulmonologist, or ear nose throat specialist to the patient’s care team is advisable in more challenging cases.

If a child is younger than 3 months and has moderate to severe atopic dermatitis, an underlying immune defect may be to blame, so an allergy and immunology assessment is warranted, Brown-Whitehorn said. “An allergist can help any child who has recurrent coughing or wheezing avoid the emergency room or hospitalization.”

“In pediatrics, we always try to find the medication, regimen, and avoidance strategies that use the least treatment to provide the best care for each patient,” Brown-Whitehorn added. “Children eat, play, learn, and sleep, and every stage of the atopic march affects each of these activities. As clinicians, we need to be sure that we are helping children make the best of all these activities.”

Brown-Whitehorn reported financial relationships with DBV Technologies and Regeneron Pharmaceuticals. Lee reported financial relationships with Novartis. Pandya reported financial relationships with DBV Technologies, Thermo Fisher Scientific, and Sanofi.
 

A version of this article first appeared on Medscape.com.

Primary care physicians (PCPs) play a key role in treating young patients as they progress through the “atopic march” from atopic dermatitis through food allergy, asthma, and allergic rhinitis. They can also help prevent the process from starting.

“The PCP is usually the first clinician a family with concerns about atopic conditions sees, unless they first visit urgent care or an emergency department after an allergic reaction to food. Either way, families rely on their PCP for ongoing guidance,” said Terri F. Brown-Whitehorn, MD, attending physician in the Division of Allergy and Immunology at the Center for Pediatric Eosinophilic Disorders and the Integrative Health Program at Children’s Hospital of Philadelphia.

“The most important thing PCPs can do is know that the atopic march exists, how it progresses over time, and what signs and symptoms to look for,” she told this news organization.
 

The Atopic March

The atopic march describes the progression of allergic diseases in a child over time, with atopic dermatitis and food allergy in infancy tending to be followed by allergic rhinitis and asthma into later childhood and adulthood.

Although the pathophysiology of the inflammation that precedes atopic dermatitis is unclear, two main hypotheses have been proposed. The first suggests a primary immune dysfunction leads to immunoglobulin E (IgE) sensitization, allergic inflammation, and a secondary disturbance of the epithelial barrier; the second starts with a primary defect in the epithelial barrier that leads to secondary immunologic dysregulation and results in inflammation.

Genetics, infection, hygiene, extreme climate, food allergens, probiotics, aeroallergens, and tobacco smoke are thought to play roles in atopic dermatitis. An estimated 10%-12% of children and 1% of adults in the United States have been reported to have the condition, and the prevalence appears to be increasing. An estimated 85% of cases occur during the first year of life and 95% before the age of 5 years.

“Atopy often, though not always, runs in families, so PCPs should inquire about the history of atopic dermatitis, IgE-mediated food allergies, allergic rhinitis, and asthma in the patient’s siblings, parents, and grandparents,” Brown-Whitehorn said.
 

Key Educators

PCPs treat the full gamut of atopic conditions and are key educators on ways families can help mitigate their children’s atopic march or stop it before it begins, said Gerald Bell Lee, MD, an allergist and immunologist at Children’s Healthcare of Atlanta and an associate professor in the Division of Allergy and Immunology at Emory University School of Medicine, Atlanta.

“Most parents who bring their infants with eczema to the PCP assume their child ate something that caused their rash. But the relationship between atopic dermatitis, a type of eczema, and food allergy is more complicated,” he added.

Lee said PCPs should explain to their patients what atopic dermatitis is, how it starts and progresses, and how families can help prevent the condition by, for example, introducing allergenic foods to infants at around 4-6 months of age.
 

Atopic Dermatitis

PCPs should inform parents and other caregivers to wash their hands before moisturizing their child, take care not to contaminate the moisturizer, and bathe their child only when the child is dirty.

“Soap removes protective natural skin oils and increases moisture loss, and exposure to soap and bathing is a main contributor to eczema,” said Lee. “Dry skin loses its protective barrier, allowing outside agents to penetrate and be identified by the immune system.”

“According to one hypothesis, parents may eat food, not wash their hands afterwards, then moisturize their baby. This unhygienic practice spreads food proteins from the adult’s meal, and possibly from contaminants present in the moisturizer, all over the baby’s body,” he added.

Lee said he and his colleagues discourage overbathing babies to minimize the risk for skin injury that begins the atopic march: “New parents are inundated with infant skincare messaging and products. But we need to weigh societal pressures against practicality and ask, ‘Is the child’s skin actually dirty?’ ”

Atopic dermatitis tends to appear on the extensor surfaces, face, and scalp in infants and around arm and leg creases in toddlers and older children. Severe forms of the condition can be more widely distributed on the body, said Aarti P. Pandya, MD, medical director of the Food Allergy Center at Children’s Mercy Kansas City and clinical assistant professor of pediatrics at the University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.
 

Avoid Triggers, Minimize Flares

Triggers of eczema are varied and common. To help minimize flares, PCPs can encourage caregivers to avoid products with fragrances or dyes, minimize the use of soaps, and completely rinse laundry detergent from clothing and household items. “Advise them to keep fingernails short and control dander, pollen, mold, household chemicals, and tobacco smoke, as well as the child’s stress and anxiety, which can also be a trigger,” Lee said.

“Skin infections from organisms such as staph, herpes, or coxsackie can also exacerbate symptoms,” Brown-Whitehorn added. “PCPs can educate caregivers to avoid all known triggers and give them an ‘action plan’ to carry out when skin flares.”
 

Food Allergies

Parents may be unaware food allergens can travel far beyond the plate, Lee said. Researchers vacuuming household bedding, carpets, furniture, and other surfaces have detected unnoticeably tiny quantities of allergenic food proteins in ordinary house dust. Touching this dust appears to provide the main exposure to those allergens.

“According to the dual exposure to allergen hypothesis, an infant’s tolerance to antigens occurs through high-dose exposure by mouth, and allergic sensitization occurs through low-dose exposure through the skin,” he said. “As young as four to six months of age, even before eating solid food, a child develops eczema, has a leaky skin barrier, comes in contact with food, and develops a food allergy.”

IgE-mediated food allergies can begin at any age. “Symptoms occur when a food is ingested and the patient develops symptoms including but not limited to urticaria, angioedema, pruritus, flushing, vomiting, diarrhea, coughing, wheezing, difficulty breathing, presyncope, or syncope,” Pandya noted.

In the case of eosinophilic esophagitis, which may also be part of the atopic march, infants and toddlers often have challenging-to-treat symptoms of reflux, while school-age children have reflux and abdominal pain, and adolescents and adults may experience difficulty swallowing and impactions of food or pills, Brown-Whitehorn said.

To differentiate between food allergy and contact dermatitis, Lee suggested providers ask, “ ’Is the rash hives? If yes, is the rash generalized or in a limited area?’ Then consider the statistical probabilities. Skin problems after milk, egg, wheat, soy, peanut, tree nut, fish, shellfish, or sesame are likely due to IgE-mediated food allergy, but after ketchup or strawberry are probably from skin contact.”
 

Allergic Rhinitis and Asthma

“For asthma, ask about frequency of night cough and symptoms with exercise, laughing, or crying. For allergic rhinitis, look for runny nose, itchy eyes, or sneezing,” Brown-Whitehorn said.

Testing and Monitoring

Assessing the extent of eczema with the Eczema Area and Severity Index or the SCORing Atopic Dermatitis index takes time but may be necessary to obtain insurance coverage for treatments such as biologics.

Avoid ordering IgE food panels, which can result in false positives that can lead to loss of tolerance and nutritional deficiencies; psychological harm from bullying, anxiety, and decreased quality of life; and higher food and healthcare costs, Pandya said.

Treatments
Caregivers may be wary about treatments, and all the three experts this news organization spoke with stressed the importance of educating caregivers about how treatments work and what to expect from them.

“Early and aggressive atopic dermatitis treatment could prevent sensitization to food or aeroallergens, which could help prevent additional atopic diseases, including those on the atopic march,” Pandya said. “Topical steroids are considered first line at any age. Topical phosphodiesterase inhibitors are approved at 3 months of age and above. Topical calcineurin inhibitors are approved at 2 years of age and above. Wet wrap therapy and bleach baths can be effective. Other options include biologic therapy, allergen immunotherapy, and UV therapy.”

“Epinephrine auto-injectors can counteract food reactions. For allergic rhinitis, non-sedating antihistamines, steroidal nasal sprays, and nasal antihistamines help. Asthma treatments include various inhaled medications,” Brown-Whitehorn added.
 

When to Refer to Specialists

Involving an allergist, dermatologist, pulmonologist, or ear nose throat specialist to the patient’s care team is advisable in more challenging cases.

If a child is younger than 3 months and has moderate to severe atopic dermatitis, an underlying immune defect may be to blame, so an allergy and immunology assessment is warranted, Brown-Whitehorn said. “An allergist can help any child who has recurrent coughing or wheezing avoid the emergency room or hospitalization.”

“In pediatrics, we always try to find the medication, regimen, and avoidance strategies that use the least treatment to provide the best care for each patient,” Brown-Whitehorn added. “Children eat, play, learn, and sleep, and every stage of the atopic march affects each of these activities. As clinicians, we need to be sure that we are helping children make the best of all these activities.”

Brown-Whitehorn reported financial relationships with DBV Technologies and Regeneron Pharmaceuticals. Lee reported financial relationships with Novartis. Pandya reported financial relationships with DBV Technologies, Thermo Fisher Scientific, and Sanofi.
 

A version of this article first appeared on Medscape.com.

Physicians shared their views on frequently discussed (and sometimes controversial) topics ranging from romances with patients to age-related competency tests in the latest report from Medscape Medical News.

The report captured data from over 1000 full- or part-time US physicians across more than 29 specialties who were surveyed over a 3-month period in 2024.

Responsibility toward their patients was a clear priority among the doctors surveyed.

While around 6 in 10 physicians said they would immediately discharge a patient who refused to follow their treatment recommendations, 8% said they would wait, and 31% indicated they would keep the patient.

Asked whether physicians should have to undergo competency testing at a certain age, 30% of respondents said yes vs 22% no, and 48% felt it depended on multiple factors.

Most doctors (91%) said they would not accept a gift of substantial monetary or sentimental value from a patient, adhering to the AMA Code of Medical Ethics.

Big gifts “may signal psychological issues, and it is not fair to patients who can’t afford big gifts, since they may encourage better care,” said Jason Doctor, PhD, a senior scholar at the USC Leonard D. Schaeffer Center for Health Policy & Economics in Los Angeles, California. “It also taints the doctor-patient relationship, which should not involve large gifts of expectations of reciprocity.”

The vast majority of doctors said a romantic relationship with a patient still in their care was unacceptable, although 1% felt it would be OK, and 9% said, “it depends.”

When asked if they might withhold information about a patient’s condition if disclosure could do more harm than good, the majority of doctors said no. But 38% said it depended on the situation.

“This is how the profession and public expectations are evolving from the old paternalistic approach,” said Peter Angood, MD, president and CEO of the American Association for Physician Leadership.

Meanwhile, most doctors (62%) said that an annual flu shot should be mandatory for physicians who see patients. And a substantial majority of doctors surveyed agreed that taking care of their physical and mental health amounts to an ethical duty.

Around three in four physicians surveyed said felt periodic bias training was necessary for doctors.

“We all need refreshers about our own bias and how to manage it,” one respondent said. But another physician said, “I think we all know what appropriate behavior is and don’t need to add yet another CME course, ugh.”

Roughly equal shares of doctors surveyed felt some obligation to take at least some Medicaid patients or felt no societal obligation. The remaining 18% were willing to treat Medicaid patients once states streamlined the rules and improved reimbursements.

And finally, nearly all the survey respondents said physicians should advise patients on the risks of marijuana, notwithstanding the number of states and localities that recently have legalized pot or cannabis products.
 

A version of this article first appeared on Medscape.com.

Physicians shared their views on frequently discussed (and sometimes controversial) topics ranging from romances with patients to age-related competency tests in the latest report from Medscape Medical News.

The report captured data from over 1000 full- or part-time US physicians across more than 29 specialties who were surveyed over a 3-month period in 2024.

Responsibility toward their patients was a clear priority among the doctors surveyed.

While around 6 in 10 physicians said they would immediately discharge a patient who refused to follow their treatment recommendations, 8% said they would wait, and 31% indicated they would keep the patient.

Asked whether physicians should have to undergo competency testing at a certain age, 30% of respondents said yes vs 22% no, and 48% felt it depended on multiple factors.

Most doctors (91%) said they would not accept a gift of substantial monetary or sentimental value from a patient, adhering to the AMA Code of Medical Ethics.

Big gifts “may signal psychological issues, and it is not fair to patients who can’t afford big gifts, since they may encourage better care,” said Jason Doctor, PhD, a senior scholar at the USC Leonard D. Schaeffer Center for Health Policy & Economics in Los Angeles, California. “It also taints the doctor-patient relationship, which should not involve large gifts of expectations of reciprocity.”

The vast majority of doctors said a romantic relationship with a patient still in their care was unacceptable, although 1% felt it would be OK, and 9% said, “it depends.”

When asked if they might withhold information about a patient’s condition if disclosure could do more harm than good, the majority of doctors said no. But 38% said it depended on the situation.

“This is how the profession and public expectations are evolving from the old paternalistic approach,” said Peter Angood, MD, president and CEO of the American Association for Physician Leadership.

Meanwhile, most doctors (62%) said that an annual flu shot should be mandatory for physicians who see patients. And a substantial majority of doctors surveyed agreed that taking care of their physical and mental health amounts to an ethical duty.

Around three in four physicians surveyed said felt periodic bias training was necessary for doctors.

“We all need refreshers about our own bias and how to manage it,” one respondent said. But another physician said, “I think we all know what appropriate behavior is and don’t need to add yet another CME course, ugh.”

Roughly equal shares of doctors surveyed felt some obligation to take at least some Medicaid patients or felt no societal obligation. The remaining 18% were willing to treat Medicaid patients once states streamlined the rules and improved reimbursements.

And finally, nearly all the survey respondents said physicians should advise patients on the risks of marijuana, notwithstanding the number of states and localities that recently have legalized pot or cannabis products.
 

A version of this article first appeared on Medscape.com.

Physicians shared their views on frequently discussed (and sometimes controversial) topics ranging from romances with patients to age-related competency tests in the latest report from Medscape Medical News.

The report captured data from over 1000 full- or part-time US physicians across more than 29 specialties who were surveyed over a 3-month period in 2024.

Responsibility toward their patients was a clear priority among the doctors surveyed.

While around 6 in 10 physicians said they would immediately discharge a patient who refused to follow their treatment recommendations, 8% said they would wait, and 31% indicated they would keep the patient.

Asked whether physicians should have to undergo competency testing at a certain age, 30% of respondents said yes vs 22% no, and 48% felt it depended on multiple factors.

Most doctors (91%) said they would not accept a gift of substantial monetary or sentimental value from a patient, adhering to the AMA Code of Medical Ethics.

Big gifts “may signal psychological issues, and it is not fair to patients who can’t afford big gifts, since they may encourage better care,” said Jason Doctor, PhD, a senior scholar at the USC Leonard D. Schaeffer Center for Health Policy & Economics in Los Angeles, California. “It also taints the doctor-patient relationship, which should not involve large gifts of expectations of reciprocity.”

The vast majority of doctors said a romantic relationship with a patient still in their care was unacceptable, although 1% felt it would be OK, and 9% said, “it depends.”

When asked if they might withhold information about a patient’s condition if disclosure could do more harm than good, the majority of doctors said no. But 38% said it depended on the situation.

“This is how the profession and public expectations are evolving from the old paternalistic approach,” said Peter Angood, MD, president and CEO of the American Association for Physician Leadership.

Meanwhile, most doctors (62%) said that an annual flu shot should be mandatory for physicians who see patients. And a substantial majority of doctors surveyed agreed that taking care of their physical and mental health amounts to an ethical duty.

Around three in four physicians surveyed said felt periodic bias training was necessary for doctors.

“We all need refreshers about our own bias and how to manage it,” one respondent said. But another physician said, “I think we all know what appropriate behavior is and don’t need to add yet another CME course, ugh.”

Roughly equal shares of doctors surveyed felt some obligation to take at least some Medicaid patients or felt no societal obligation. The remaining 18% were willing to treat Medicaid patients once states streamlined the rules and improved reimbursements.

And finally, nearly all the survey respondents said physicians should advise patients on the risks of marijuana, notwithstanding the number of states and localities that recently have legalized pot or cannabis products.
 

A version of this article first appeared on Medscape.com.

Depending on one’s perspective, “mast cell activation syndrome (MCAS)” is either a relatively rare, narrowly defined severe allergic condition or a vastly underrecognized underlying cause of multiple chronic inflammatory conditions that affect roughly 17% of the entire population. 

Inappropriate activation of mast cells — now termed mast cell activation disease (MCAD) — has long been known to underlie allergic symptoms and inflammation, and far less commonly, neoplasias such as mastocytosis. The concept of chronic, persistent MCAS associated with aberrant growth and dystrophism is more recent, emerging only in the last couple of decades as a separate entity under the MCAD heading. 

Observational studies and clinical experience have linked signs and symptoms of MCAS with other inflammatory chronic conditions such as hypermobile Ehlers-Danlos Syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and recently, long COVID. However, those conditions themselves are diagnostically challenging, and as yet there is no proof of causation.

The idea that MCAS is the entity — or at least, a key one — at the center of “a confoundingly, extraordinarily heterogeneous chronic multisystem polymorbidity” was the theme of a recent 4-day meeting of a professional group informally dubbed “Masterminds.” Since their first meeting in 2018, the group has grown from about 35 to nearly 650 multidisciplinary professionals. 

Stephanie L. Grach, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minnesota, gave an introductory talk about the importance of changing “the medical paradigm around complex chronic illness.” Much of the rest of the meeting was devoted to sharing approaches for managing MCAS comorbidities, including dysautonomia, hypermobility, and associated craniocervical dysfunction, and various other multi-system conditions characterized by chronic pain and/or fatigue. Several talks covered the use of agents that block mast cell activity as potential treatment. 

In an interview, Grach said “the meeting was an exciting example of how not only research, but also medicine, is moving forward, and it’s really cool to see that people are independently coming to very similar conclusions about shared pathologies, and because of that, the importance of overlap amongst complex medical conditions that historically have really been poorly addressed.”

She added, “mast cell activation, or mast cell hyperactivity, is one part of the greater picture. What’s important about the mast cell component is that of the multiple different targetable pathologies, it’s one that currently has potential available therapies that can be explored, some of them relatively easily.”

But Christopher Chang, MD, PhD, chief of the Pediatric Allergy and Immunology program, Joe DiMaggio Children’s Hospital, Hollywood, Florida, sees it differently. In an interview, he noted that the reason for disagreement over what constitutes MCAS is that “it doesn’t have a lot of objective findings that we can identify. ... We know that mast cells are important immune cells, just like all immune cells are important. It seems like whenever someone has unexplained symptoms, people try to blame it on mast cells. But it’s very hard to prove that.” 
 

Two Definitions Characterize the Illness Differently

One proposed “consensus” MCAS definition was first published in 2011 by a group led by hematologist Peter Valent, MD, of the Medical University of Vienna in Austria. It has been revised since, and similar versions adopted by medical societies, including the American Academy of Allergy, Asthma & Immunology (AAAAI). The most recent versions propose three core MCAS criteria: 

• Typical clinical signs of severe, recurrent (episodic) systemic (at least two organ systems) MCA are present (often in the form of anaphylaxis).
• The involvement of mast cells (MCs) is documented by biochemical studies, preferably an increase in serum tryptase levels from the individual’s baseline to plus 20% + 2 ng/mL.
• Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production, or drugs blocking mediator release or effects of MC-derived mediators.

The following year, a separate publication authored by Gerhard J. Molderings, MD, University of Bonn in Germany, and colleagues proposed a much broader MCAS definition. Also revised since, the latest “consensus-2” was published in 2020. This definition consists of one major criterion: “A constellation of clinical complaints attributable to pathologically increased MC activity, ie, MC mediator release syndrome.” This “constellation” involves conditions of nearly every organ system that, taken together, are estimated to affect up to 17% of the entire population. These are just a few examples: 

• Constitutional: Chronic fatigue, flushing, or sweats
• Dermatologic: Rashes or lesions
• Ophthalmologic: dry eyes
• Oral: Burning or itching in mouth
• Pulmonary: Airway inflammation at any/all levels
• Cardiovascular: Blood pressure lability or codiagnosis of POTS is common
• Gastrointestinal: Reflux, dysphagia, or malabsorption
• Genitourinary: Endometriosis, dysmenorrhea, or dyspareunia
• Musculoskeletal/connective tissue: Fibromyalgia or diagnosis of hypermobile EDS is common
• Neurologic: Headaches or sensory neuropathies
• Psychiatric: Depression or anxiety
• Endocrinologic: Thyroid disease or dyslipidemia
• Hematologic: Polycythemia or anemia (after ruling out other causes)

The diagnosis is made by fulfilling that major criterion, plus at least one objective assessment of pathologically increased release of MC mediators, including infiltrates, abnormal MC morphology, or MC genetic changes shown to increase MC activity. Other alternatives include evidence of above-normal levels of MC mediators, including tryptase, histamine or its metabolites, heparin, or chromatin A, in whole blood, serum, plasma, or urine. Symptomatic response to MC activation inhibitors can also be used but isn’t required as it is in the other definition. 
 

Underdiagnosis vs Overdiagnosis

Lawrence B. Afrin, MD, senior consultant in hematology/oncology at the AIM Center for Personalized Medicine, Westchester, New York, and lead author of the 2020 update of the broader “consensus-2” criteria, said in an interview, “we now know MCAS exists, and it’s prevalent, even though, for understandable and forgivable reasons, we’ve been missing it all along. ... If you see a patient who has this chronic, multisystem unwellness with general themes of inflammation plus or minus allergic issues and you can’t find some other rational explanation that better accounts for what’s going on ... then it’s reasonable to think to include MCAS in the differential diagnosis. If the patient happens not to fit the diagnostic criteria being advanced by one group, that doesn’t necessarily rule out the possibility that this is still going on.”

Afrin, along with his coauthors, faulted the narrower “consensus-1” definition for lacking data to support the “20% + 2” criteria for requiring the difficult determination of a patient’s “baseline” and for requiring evidence of response to treatment prior to making the diagnosis. Not all patients will respond to a given histamine blocker, he noted. 

But Lawrence B. Schwartz, MD, PhD, an author on both the Valent and AAAAI criteria, disagreed, noting that the narrower criteria “appear to have a high degree of specificity and sensitivity when the reaction is systemic and involves hypotension. Less severe clinical events, particularly involving the gastrointestinal or central nervous systems, do not have precise clinical or biomarker criteria for identifying mast cell involvement.” 

Added Schwartz, who is professor of medicine and chair of the Division of Rheumatology, Allergy, and Immunology and program director of Allergy and Immunology, Virginia Commonwealth University (VCU), Richmond, “when mast cell activation events occur only in the skin, we refer to it as chronic urticaria and in the airways or conjunctiva of allergic individuals as allergic asthma, rhinitis, and/or conjunctivitis. The absence of specific criteria for mast cell activation in the GI [gastrointestinal] tract or CNS [central nervous system] neither rules in mast cell involvement nor does it rule out mast cell involvement. Thus, more research is needed to find better diagnostic criteria.”

Schwartz also pointed to a recent paper reporting the use of artificial intelligence models to “quantify diagnostic precision and specificity” of “alternative” MCAS definitions. The conclusion was a “lack of specificity is pronounced in relation to multiple control criteria, raising the concern that alternative criteria could disproportionately contribute to MCAS overdiagnosis, to the exclusion of more appropriate diagnoses.”

During the meeting, Afrin acknowledged that the broader view risks overdiagnosis of MCAS. However, he also referenced Occam’s razor, the principle that the simplest explanation is probably the best one. “Which scenario is more likely? Multiple diagnoses and problems that are all independent of each other vs one diagnosis that’s biologically capable of causing most or all of the findings, ie, the simplest solution even if it’s not the most immediately obvious solution?”

He said in an interview: “Do we have any proof that MCAS is what’s underlying hypermobile Ehlers-Danlos or POTS or chronic fatigue? No, we don’t have any proof, not because anybody has done studies that have shown there to be no connection but simply because we’re so early in our awareness that the disease even exists that the necessary studies haven’t even been done yet.”

At the meeting, Afrin introduced proposals to turn the “Masterminds” group into a formal professional society and to launch a journal. He also gave an update on progress in developing a symptom assessment tool both for clinical use and to enable clinical trials of new drugs to target mast cells or their mediators. The plan is to field test the tool in 2025 and publish those results in 2026. 

Grach, Afrin, and Chang had no disclosures. Schwartz discovered tryptase and invented the Thermo Fisher tryptase assay, for which his institution (VCU) receives royalties that are shared with him. He also invented monoclonal antibodies used for detecting mast cells or basophils, for which VCU receives royalties from several companies, including Millipore, Santa Cruz, BioLegend, and Hycult Biotech, that are also shared with him. He is a paid consultant for Blueprint Medicines, Celldex Therapeutics, Invea, Third Harmonic Bio, HYCOR Biomedical, Jasper, TerSera Therapeutics, and GLG. He also serves on an AstraZeneca data safety monitoring board for a clinical trial involving benralizumab treatment of hypereosinophilic syndrome and receives royalties from UpToDate (biomarkers for anaphylaxis) and Goldman-Cecil Medicine (anaphylaxis).

A version of this article first appeared on Medscape.com.

Depending on one’s perspective, “mast cell activation syndrome (MCAS)” is either a relatively rare, narrowly defined severe allergic condition or a vastly underrecognized underlying cause of multiple chronic inflammatory conditions that affect roughly 17% of the entire population. 

Inappropriate activation of mast cells — now termed mast cell activation disease (MCAD) — has long been known to underlie allergic symptoms and inflammation, and far less commonly, neoplasias such as mastocytosis. The concept of chronic, persistent MCAS associated with aberrant growth and dystrophism is more recent, emerging only in the last couple of decades as a separate entity under the MCAD heading. 

Observational studies and clinical experience have linked signs and symptoms of MCAS with other inflammatory chronic conditions such as hypermobile Ehlers-Danlos Syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and recently, long COVID. However, those conditions themselves are diagnostically challenging, and as yet there is no proof of causation.

The idea that MCAS is the entity — or at least, a key one — at the center of “a confoundingly, extraordinarily heterogeneous chronic multisystem polymorbidity” was the theme of a recent 4-day meeting of a professional group informally dubbed “Masterminds.” Since their first meeting in 2018, the group has grown from about 35 to nearly 650 multidisciplinary professionals. 

Stephanie L. Grach, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minnesota, gave an introductory talk about the importance of changing “the medical paradigm around complex chronic illness.” Much of the rest of the meeting was devoted to sharing approaches for managing MCAS comorbidities, including dysautonomia, hypermobility, and associated craniocervical dysfunction, and various other multi-system conditions characterized by chronic pain and/or fatigue. Several talks covered the use of agents that block mast cell activity as potential treatment. 

In an interview, Grach said “the meeting was an exciting example of how not only research, but also medicine, is moving forward, and it’s really cool to see that people are independently coming to very similar conclusions about shared pathologies, and because of that, the importance of overlap amongst complex medical conditions that historically have really been poorly addressed.”

She added, “mast cell activation, or mast cell hyperactivity, is one part of the greater picture. What’s important about the mast cell component is that of the multiple different targetable pathologies, it’s one that currently has potential available therapies that can be explored, some of them relatively easily.”

But Christopher Chang, MD, PhD, chief of the Pediatric Allergy and Immunology program, Joe DiMaggio Children’s Hospital, Hollywood, Florida, sees it differently. In an interview, he noted that the reason for disagreement over what constitutes MCAS is that “it doesn’t have a lot of objective findings that we can identify. ... We know that mast cells are important immune cells, just like all immune cells are important. It seems like whenever someone has unexplained symptoms, people try to blame it on mast cells. But it’s very hard to prove that.” 
 

Two Definitions Characterize the Illness Differently

One proposed “consensus” MCAS definition was first published in 2011 by a group led by hematologist Peter Valent, MD, of the Medical University of Vienna in Austria. It has been revised since, and similar versions adopted by medical societies, including the American Academy of Allergy, Asthma & Immunology (AAAAI). The most recent versions propose three core MCAS criteria: 

• Typical clinical signs of severe, recurrent (episodic) systemic (at least two organ systems) MCA are present (often in the form of anaphylaxis).
• The involvement of mast cells (MCs) is documented by biochemical studies, preferably an increase in serum tryptase levels from the individual’s baseline to plus 20% + 2 ng/mL.
• Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production, or drugs blocking mediator release or effects of MC-derived mediators.

The following year, a separate publication authored by Gerhard J. Molderings, MD, University of Bonn in Germany, and colleagues proposed a much broader MCAS definition. Also revised since, the latest “consensus-2” was published in 2020. This definition consists of one major criterion: “A constellation of clinical complaints attributable to pathologically increased MC activity, ie, MC mediator release syndrome.” This “constellation” involves conditions of nearly every organ system that, taken together, are estimated to affect up to 17% of the entire population. These are just a few examples: 

• Constitutional: Chronic fatigue, flushing, or sweats
• Dermatologic: Rashes or lesions
• Ophthalmologic: dry eyes
• Oral: Burning or itching in mouth
• Pulmonary: Airway inflammation at any/all levels
• Cardiovascular: Blood pressure lability or codiagnosis of POTS is common
• Gastrointestinal: Reflux, dysphagia, or malabsorption
• Genitourinary: Endometriosis, dysmenorrhea, or dyspareunia
• Musculoskeletal/connective tissue: Fibromyalgia or diagnosis of hypermobile EDS is common
• Neurologic: Headaches or sensory neuropathies
• Psychiatric: Depression or anxiety
• Endocrinologic: Thyroid disease or dyslipidemia
• Hematologic: Polycythemia or anemia (after ruling out other causes)

The diagnosis is made by fulfilling that major criterion, plus at least one objective assessment of pathologically increased release of MC mediators, including infiltrates, abnormal MC morphology, or MC genetic changes shown to increase MC activity. Other alternatives include evidence of above-normal levels of MC mediators, including tryptase, histamine or its metabolites, heparin, or chromatin A, in whole blood, serum, plasma, or urine. Symptomatic response to MC activation inhibitors can also be used but isn’t required as it is in the other definition. 
 

Underdiagnosis vs Overdiagnosis

Lawrence B. Afrin, MD, senior consultant in hematology/oncology at the AIM Center for Personalized Medicine, Westchester, New York, and lead author of the 2020 update of the broader “consensus-2” criteria, said in an interview, “we now know MCAS exists, and it’s prevalent, even though, for understandable and forgivable reasons, we’ve been missing it all along. ... If you see a patient who has this chronic, multisystem unwellness with general themes of inflammation plus or minus allergic issues and you can’t find some other rational explanation that better accounts for what’s going on ... then it’s reasonable to think to include MCAS in the differential diagnosis. If the patient happens not to fit the diagnostic criteria being advanced by one group, that doesn’t necessarily rule out the possibility that this is still going on.”

Afrin, along with his coauthors, faulted the narrower “consensus-1” definition for lacking data to support the “20% + 2” criteria for requiring the difficult determination of a patient’s “baseline” and for requiring evidence of response to treatment prior to making the diagnosis. Not all patients will respond to a given histamine blocker, he noted. 

But Lawrence B. Schwartz, MD, PhD, an author on both the Valent and AAAAI criteria, disagreed, noting that the narrower criteria “appear to have a high degree of specificity and sensitivity when the reaction is systemic and involves hypotension. Less severe clinical events, particularly involving the gastrointestinal or central nervous systems, do not have precise clinical or biomarker criteria for identifying mast cell involvement.” 

Added Schwartz, who is professor of medicine and chair of the Division of Rheumatology, Allergy, and Immunology and program director of Allergy and Immunology, Virginia Commonwealth University (VCU), Richmond, “when mast cell activation events occur only in the skin, we refer to it as chronic urticaria and in the airways or conjunctiva of allergic individuals as allergic asthma, rhinitis, and/or conjunctivitis. The absence of specific criteria for mast cell activation in the GI [gastrointestinal] tract or CNS [central nervous system] neither rules in mast cell involvement nor does it rule out mast cell involvement. Thus, more research is needed to find better diagnostic criteria.”

Schwartz also pointed to a recent paper reporting the use of artificial intelligence models to “quantify diagnostic precision and specificity” of “alternative” MCAS definitions. The conclusion was a “lack of specificity is pronounced in relation to multiple control criteria, raising the concern that alternative criteria could disproportionately contribute to MCAS overdiagnosis, to the exclusion of more appropriate diagnoses.”

During the meeting, Afrin acknowledged that the broader view risks overdiagnosis of MCAS. However, he also referenced Occam’s razor, the principle that the simplest explanation is probably the best one. “Which scenario is more likely? Multiple diagnoses and problems that are all independent of each other vs one diagnosis that’s biologically capable of causing most or all of the findings, ie, the simplest solution even if it’s not the most immediately obvious solution?”

He said in an interview: “Do we have any proof that MCAS is what’s underlying hypermobile Ehlers-Danlos or POTS or chronic fatigue? No, we don’t have any proof, not because anybody has done studies that have shown there to be no connection but simply because we’re so early in our awareness that the disease even exists that the necessary studies haven’t even been done yet.”

At the meeting, Afrin introduced proposals to turn the “Masterminds” group into a formal professional society and to launch a journal. He also gave an update on progress in developing a symptom assessment tool both for clinical use and to enable clinical trials of new drugs to target mast cells or their mediators. The plan is to field test the tool in 2025 and publish those results in 2026. 

Grach, Afrin, and Chang had no disclosures. Schwartz discovered tryptase and invented the Thermo Fisher tryptase assay, for which his institution (VCU) receives royalties that are shared with him. He also invented monoclonal antibodies used for detecting mast cells or basophils, for which VCU receives royalties from several companies, including Millipore, Santa Cruz, BioLegend, and Hycult Biotech, that are also shared with him. He is a paid consultant for Blueprint Medicines, Celldex Therapeutics, Invea, Third Harmonic Bio, HYCOR Biomedical, Jasper, TerSera Therapeutics, and GLG. He also serves on an AstraZeneca data safety monitoring board for a clinical trial involving benralizumab treatment of hypereosinophilic syndrome and receives royalties from UpToDate (biomarkers for anaphylaxis) and Goldman-Cecil Medicine (anaphylaxis).

A version of this article first appeared on Medscape.com.

Depending on one’s perspective, “mast cell activation syndrome (MCAS)” is either a relatively rare, narrowly defined severe allergic condition or a vastly underrecognized underlying cause of multiple chronic inflammatory conditions that affect roughly 17% of the entire population. 

Inappropriate activation of mast cells — now termed mast cell activation disease (MCAD) — has long been known to underlie allergic symptoms and inflammation, and far less commonly, neoplasias such as mastocytosis. The concept of chronic, persistent MCAS associated with aberrant growth and dystrophism is more recent, emerging only in the last couple of decades as a separate entity under the MCAD heading. 

Observational studies and clinical experience have linked signs and symptoms of MCAS with other inflammatory chronic conditions such as hypermobile Ehlers-Danlos Syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and recently, long COVID. However, those conditions themselves are diagnostically challenging, and as yet there is no proof of causation.

The idea that MCAS is the entity — or at least, a key one — at the center of “a confoundingly, extraordinarily heterogeneous chronic multisystem polymorbidity” was the theme of a recent 4-day meeting of a professional group informally dubbed “Masterminds.” Since their first meeting in 2018, the group has grown from about 35 to nearly 650 multidisciplinary professionals. 

Stephanie L. Grach, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minnesota, gave an introductory talk about the importance of changing “the medical paradigm around complex chronic illness.” Much of the rest of the meeting was devoted to sharing approaches for managing MCAS comorbidities, including dysautonomia, hypermobility, and associated craniocervical dysfunction, and various other multi-system conditions characterized by chronic pain and/or fatigue. Several talks covered the use of agents that block mast cell activity as potential treatment. 

In an interview, Grach said “the meeting was an exciting example of how not only research, but also medicine, is moving forward, and it’s really cool to see that people are independently coming to very similar conclusions about shared pathologies, and because of that, the importance of overlap amongst complex medical conditions that historically have really been poorly addressed.”

She added, “mast cell activation, or mast cell hyperactivity, is one part of the greater picture. What’s important about the mast cell component is that of the multiple different targetable pathologies, it’s one that currently has potential available therapies that can be explored, some of them relatively easily.”

But Christopher Chang, MD, PhD, chief of the Pediatric Allergy and Immunology program, Joe DiMaggio Children’s Hospital, Hollywood, Florida, sees it differently. In an interview, he noted that the reason for disagreement over what constitutes MCAS is that “it doesn’t have a lot of objective findings that we can identify. ... We know that mast cells are important immune cells, just like all immune cells are important. It seems like whenever someone has unexplained symptoms, people try to blame it on mast cells. But it’s very hard to prove that.” 
 

Two Definitions Characterize the Illness Differently

One proposed “consensus” MCAS definition was first published in 2011 by a group led by hematologist Peter Valent, MD, of the Medical University of Vienna in Austria. It has been revised since, and similar versions adopted by medical societies, including the American Academy of Allergy, Asthma & Immunology (AAAAI). The most recent versions propose three core MCAS criteria: 

• Typical clinical signs of severe, recurrent (episodic) systemic (at least two organ systems) MCA are present (often in the form of anaphylaxis).
• The involvement of mast cells (MCs) is documented by biochemical studies, preferably an increase in serum tryptase levels from the individual’s baseline to plus 20% + 2 ng/mL.
• Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production, or drugs blocking mediator release or effects of MC-derived mediators.

The following year, a separate publication authored by Gerhard J. Molderings, MD, University of Bonn in Germany, and colleagues proposed a much broader MCAS definition. Also revised since, the latest “consensus-2” was published in 2020. This definition consists of one major criterion: “A constellation of clinical complaints attributable to pathologically increased MC activity, ie, MC mediator release syndrome.” This “constellation” involves conditions of nearly every organ system that, taken together, are estimated to affect up to 17% of the entire population. These are just a few examples: 

• Constitutional: Chronic fatigue, flushing, or sweats
• Dermatologic: Rashes or lesions
• Ophthalmologic: dry eyes
• Oral: Burning or itching in mouth
• Pulmonary: Airway inflammation at any/all levels
• Cardiovascular: Blood pressure lability or codiagnosis of POTS is common
• Gastrointestinal: Reflux, dysphagia, or malabsorption
• Genitourinary: Endometriosis, dysmenorrhea, or dyspareunia
• Musculoskeletal/connective tissue: Fibromyalgia or diagnosis of hypermobile EDS is common
• Neurologic: Headaches or sensory neuropathies
• Psychiatric: Depression or anxiety
• Endocrinologic: Thyroid disease or dyslipidemia
• Hematologic: Polycythemia or anemia (after ruling out other causes)

The diagnosis is made by fulfilling that major criterion, plus at least one objective assessment of pathologically increased release of MC mediators, including infiltrates, abnormal MC morphology, or MC genetic changes shown to increase MC activity. Other alternatives include evidence of above-normal levels of MC mediators, including tryptase, histamine or its metabolites, heparin, or chromatin A, in whole blood, serum, plasma, or urine. Symptomatic response to MC activation inhibitors can also be used but isn’t required as it is in the other definition. 
 

Underdiagnosis vs Overdiagnosis

Lawrence B. Afrin, MD, senior consultant in hematology/oncology at the AIM Center for Personalized Medicine, Westchester, New York, and lead author of the 2020 update of the broader “consensus-2” criteria, said in an interview, “we now know MCAS exists, and it’s prevalent, even though, for understandable and forgivable reasons, we’ve been missing it all along. ... If you see a patient who has this chronic, multisystem unwellness with general themes of inflammation plus or minus allergic issues and you can’t find some other rational explanation that better accounts for what’s going on ... then it’s reasonable to think to include MCAS in the differential diagnosis. If the patient happens not to fit the diagnostic criteria being advanced by one group, that doesn’t necessarily rule out the possibility that this is still going on.”

Afrin, along with his coauthors, faulted the narrower “consensus-1” definition for lacking data to support the “20% + 2” criteria for requiring the difficult determination of a patient’s “baseline” and for requiring evidence of response to treatment prior to making the diagnosis. Not all patients will respond to a given histamine blocker, he noted. 

But Lawrence B. Schwartz, MD, PhD, an author on both the Valent and AAAAI criteria, disagreed, noting that the narrower criteria “appear to have a high degree of specificity and sensitivity when the reaction is systemic and involves hypotension. Less severe clinical events, particularly involving the gastrointestinal or central nervous systems, do not have precise clinical or biomarker criteria for identifying mast cell involvement.” 

Added Schwartz, who is professor of medicine and chair of the Division of Rheumatology, Allergy, and Immunology and program director of Allergy and Immunology, Virginia Commonwealth University (VCU), Richmond, “when mast cell activation events occur only in the skin, we refer to it as chronic urticaria and in the airways or conjunctiva of allergic individuals as allergic asthma, rhinitis, and/or conjunctivitis. The absence of specific criteria for mast cell activation in the GI [gastrointestinal] tract or CNS [central nervous system] neither rules in mast cell involvement nor does it rule out mast cell involvement. Thus, more research is needed to find better diagnostic criteria.”

Schwartz also pointed to a recent paper reporting the use of artificial intelligence models to “quantify diagnostic precision and specificity” of “alternative” MCAS definitions. The conclusion was a “lack of specificity is pronounced in relation to multiple control criteria, raising the concern that alternative criteria could disproportionately contribute to MCAS overdiagnosis, to the exclusion of more appropriate diagnoses.”

During the meeting, Afrin acknowledged that the broader view risks overdiagnosis of MCAS. However, he also referenced Occam’s razor, the principle that the simplest explanation is probably the best one. “Which scenario is more likely? Multiple diagnoses and problems that are all independent of each other vs one diagnosis that’s biologically capable of causing most or all of the findings, ie, the simplest solution even if it’s not the most immediately obvious solution?”

He said in an interview: “Do we have any proof that MCAS is what’s underlying hypermobile Ehlers-Danlos or POTS or chronic fatigue? No, we don’t have any proof, not because anybody has done studies that have shown there to be no connection but simply because we’re so early in our awareness that the disease even exists that the necessary studies haven’t even been done yet.”

At the meeting, Afrin introduced proposals to turn the “Masterminds” group into a formal professional society and to launch a journal. He also gave an update on progress in developing a symptom assessment tool both for clinical use and to enable clinical trials of new drugs to target mast cells or their mediators. The plan is to field test the tool in 2025 and publish those results in 2026. 

Grach, Afrin, and Chang had no disclosures. Schwartz discovered tryptase and invented the Thermo Fisher tryptase assay, for which his institution (VCU) receives royalties that are shared with him. He also invented monoclonal antibodies used for detecting mast cells or basophils, for which VCU receives royalties from several companies, including Millipore, Santa Cruz, BioLegend, and Hycult Biotech, that are also shared with him. He is a paid consultant for Blueprint Medicines, Celldex Therapeutics, Invea, Third Harmonic Bio, HYCOR Biomedical, Jasper, TerSera Therapeutics, and GLG. He also serves on an AstraZeneca data safety monitoring board for a clinical trial involving benralizumab treatment of hypereosinophilic syndrome and receives royalties from UpToDate (biomarkers for anaphylaxis) and Goldman-Cecil Medicine (anaphylaxis).

A version of this article first appeared on Medscape.com.